Chris Jacobs

Dr Chris Jacobs

Associate Professor, Genetic and Genomic Counselling
PhD, MSc, BSc Hons



Research interests


Completed postgraduate research projects I have supervised


Aideen M McInerney-Leo, Samantha Ayres, Jackie Boyle, Chris Jacobs, Ainsley J Newson (2023)Human Genetics Society of Australasia Position Statement: Genetic Testing and Personal Insurance Products in Australia - CORRIGENDUM, In: Twin research and human geneticspp. 1-1

The expansion of genetic and genomic testing in clinical practice and research, and the growing market for direct-to-consumer genomic testing has led to increased awareness about the impact of this form of testing on insurance. Genetic or genomic information can be requested by providers of mutually rated insurance products, who may then use it when setting premiums or determining eligibility for cover under a particular product. Australian insurers are subject to relevant legislation and an industry led standard that was updated in 2019 to introduce a moratorium on the use of genetic test results in life insurance underwriting for policies

Chris Jacobs, Christine Patch (2013)Identifying individuals who might benefit from genetic services and information, In: Nursing standard28(9)pp. 37-42

This is the second in a series of articles on genetics. This article focuses on competency 1 of the revised framework for genetics/genomics for nurses. The authors discuss the importance of nurses identifying individuals who may benefit from genetic services. Recording a family history and drawing a family tree are useful skills that will help to identify these individuals and inform the healthcare team. The article explains when to refer individuals to genetic services and what they may expect from these referrals.

S. Goff, C. Jacobs, L. Robinson, P. Webb (2010)Cancer genetics, In: European journal of cancer care19(4)pp. 424-424
Lucy Bryant, Andrew Bluff, Diana Barnett, Bronwyn Hemsley, Vincent Nguyen, Christine June Jacobs, Emma Power, Benjamin Bailey, Peter Stubbs, Cherie Lucas (2020)Opportunities for the Implementation of Immersive Virtual Reality in Rehabilitation, In: Proceedings of the 53rd Hawaii International Conference of System Sciences 2020pp. 3567-3576

Virtual reality (VR) technologies are emerging as novel platforms for physical and cognitive interventions, though applications in communication rehabilitation are scarce. Consultation with end-users on implementation of VR in clinical contexts is a vital first step to investigating the feasibility VR in communication rehabilitation. The aim of this study was to explore the views of professionals with expertise in health, rehabilitation, and VR technology, on the populations that might benefit from VR-based rehabilitation, and potential barriers and facilitators to their use of VR. Thematic content analysis of one interdisciplinary focus group and one in-depth interview identified two content themes relating to the use of VR in rehabilitation, and four themes related to the use of VR to maximize its clinical benefit and uptake. Consideration of these results in the development of VR programs in rehabilitation might lead to better acceptance and implementation of VR for improved health and participation outcomes.

Ebony Richardson, Alison McEwen, Toby Newton-John, Ashley Crook, Chris Jacobs (2022)Correction: Incorporating patient perspectives in the development of a core outcome set for reproductive genetic carrier screening: a sequential systematic review, In: European journal of human genetics : EJHG30(7)pp. 866-867
April Morrow, Chris Jacobs, Megan Best, Sian Greening, Kathy Tucker (2018)Genetics in palliative oncology: a missing agenda? A review of the literature and future directions, In: Supportive care in cancer26(3)721pp. 721-730

In the palliative oncology setting, genetic assessment may not impact on the patient's management but can be of vital importance to their surviving relatives. Despite care of the family being central to the ethos of palliative care, little is known about how hereditary aspects of cancer are addressed in this setting. This review aims to examine current practices, identify practice barriers and determine the genetic information and support needs of patients, family members and health providers. Key databases were systematically searched to identify both quantitative and qualitative studies that addressed these aims. Data was extracted and coded using thematic analysis. Eight studies were included for review. Suboptimal genetic practices were identified, with lack of knowledge and poor confidence amongst providers reported as barriers in both qualitative and quantitative studies. Providers expressed concern about the emotional impact of initiating these discussions late in the disease trajectory; however, qualitative interviews amongst palliative patients suggested there may be emotional benefits. All lines of evidence suggest that genetics is currently missing from the palliative agenda, signifying lost opportunities for mutation detection, genetic counselling and appropriate risk management for surviving relatives. There is an urgent need for interventions to improve provider knowledge and awareness of genetic referral pathways and for research into the genetic information and support needs of palliative care patients.

A Bish, S Sutton, C Jacobs, S Levene, A Ramirez, S Hodgson (2002)Changes in psychological distress after cancer genetic counselling: a comparison of affected and unaffected women, In: British journal of cancer86(1)43pp. 43-50 Nature Publishing Group

This study sought to examine changes in psychological distress following cancer genetic counselling. Women attending a family cancer clinic completed questionnaires before their appointment and at 2 weeks, 6 months and 12 months after their appointment. Twenty-six women were at low risk of developing breast or ovarian cancer, 76 were at moderate risk, 46 were at high risk and 46 women had previously had breast or ovarian cancer. All groups were compared with regard to measures of anxiety, depression, general psychological distress, worry about developing breast and ovarian cancer, and perceived risk of developing breast/ovarian cancer and perceived likelihood of carrying a genetic mutation. General psychological distress did not change over the course of the study and the groups did not differ on these measures. Worry about developing breast cancer and perceptions of the likelihood of carrying a genetic mutation significantly reduced following genetic counselling. On the whole women who had already had breast/ovarian cancer showed more concerns about ovarian cancer and raised perceptions of risk in comparison with the other groups, indicating the need for sensitive counselling of such women. British Journal of Cancer (2002) 86 , 43–50. DOI: 10.1038/sj/bjc/6600030 © 2002 The Cancer Research Campaign

Emily DeBortoli, Aideen M. McInerney-Leo, Samantha Ayres, Jackie Boyle, Chris Jacobs, Ainsley J. Newson, (2023)Human Genetics Society of Australasia Position Statement: Genetic Testing and Personal Insurance Products in Australia, In: Twin research and human genetics26(2)1832427423000117pp. 184-187 Cambridge University Press

The expansion of genetic and genomic testing in clinical practice and research, and the growing market for direct-to-consumer genomic testing has led to increased awareness about the impact of this form of testing on insurance. Genetic or genomic information can be requested by providers of mutually rated insurance products, who may then use it when setting premiums or determining eligibility for cover under a particular product. Australian insurers are subject to relevant legislation and an industry led standard that was updated in 2019 to introduce a moratorium on the use of genetic test results in life insurance underwriting for policies

Ranjit Manchanda, Kelly Loggenberg, Saskia Sanderson, Matthew Burnell, Jane Wardle, Sue Gessler, Lucy Side, Nyala Balogun, Rakshit Desai, Ajith Kumar, Huw Dorkins, Yvonne Wallis, Cyril Chapman, Rohan Taylor, Chris Jacobs, Ian Tomlinson, Alistair McGuire, Uziel Beller, Usha Menon, Ian Jacobs (2015)Population Testing for Cancer Predisposing BRCA1/BRCA2 Mutations in the Ashkenazi-Jewish Community: A Randomized Controlled Trial, In: JNCI : Journal of the National Cancer Institute107(1)379pp. 379-379 Oxford Univ Press

Technological advances raise the possibility of systematic population-based genetic testing for cancer-predisposing mutations, but it is uncertain whether benefits outweigh disadvantages. We directly compared the psychological/quality-of-life consequences of such an approach to family history (FH)-based testing. In a randomized controlled trial of BRCA1/2 gene-mutation testing in the Ashkenazi Jewish (AJ) population, we compared testing all participants in the population screening (PS) arm with testing those fulfilling standard FH-based clinical criteria (FH arm). Following a targeted community campaign, AJ participants older than 18 years were recruited by self-referral after pretest genetic counseling. The effects of BRCA1/2 genetic testing on acceptability, psychological impact, and quality-of-life measures were assessed by random effects regression analysis. All statistical tests were two-sided. One thousand, one hundred sixty-eight AJ individuals were counseled, 1042 consented, 1034 were randomly assigned (691 women, 343 men), and 1017 were eligible for analysis. Mean age was 54.3 (SD = 14.66) years. Thirteen BRCA1/2 carriers were identified in the PS arm, nine in the FH arm. Five more carriers were detected among FH-negative FH-arm participants following study completion. There were no statistically significant differences between the FH and PS arms at seven days or three months on measures of anxiety, depression, health anxiety, distress, uncertainty, and quality-of-life. Contrast tests indicated that overall anxiety (P = .0001) and uncertainty (P = .005) associated with genetic testing decreased; positive experience scores increased (P = .0001); quality-of-life and health anxiety did not change with time. Overall, 56% of carriers did not fulfill clinical criteria for genetic testing, and the BRCA1/2 prevalence was 2.45%. Compared with FH-based testing, population-based genetic testing in Ashkenazi Jews doesn't adversely affect short-term psychological/quality-of-life outcomes and may detect 56% additional BRCA carriers.

Ebony Richardson, Alison McEwen, Toby Newton-John, Ashley Crook, Chris Jacobs (2022)Systematic review of outcomes in studies of reproductive genetic carrier screening: Towards development of a core outcome set, In: Genetics in medicine24(1)pp. 1-14 Elsevier

Purpose: Current practice recommendations support the widespread implementation of reproductive genetic carrier screening (RGCS). These consensus-based recommendations highlight a research gap, with findings from current studies being insufficient to meet the standard required for more rigorous evidence-based recommendations. This systematic review assessed methodological aspects of studies on RGCS to inform the need for a core outcome set. Methods: We conducted a systematic search to identify peer-reviewed published studies offering population-based RGCS. Study designs, outcomes, and measurement methods were extracted. A narrative synthesis was conducting using an existing outcome taxonomy and criteria used in the evaluation of genetic screening programs as frameworks. Results: Sixty-five publications were included. We extracted 120 outcomes representing 24 outcome domains. Heterogeneity in outcome selection, measurement methods and time points of assessment was extensive. Quality appraisal raised concerns for bias. We found that reported outcomes had limited applicability to criteria used to evaluate genetic screening programs. Conclusion: Despite a large body of literature, diverse approaches to research have limited the conclusions that can be cumulatively drawn from this body of evidence. Consensus regarding meaningful outcomes for evaluation of RGCS would be a valuable first step in working towards evidence-based practice recommendations, supporting the development of a core outcome set. (C) 2021 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics.

Alison McEwen, Chris Jacobs (2021)Preparing the genetic counseling workforce for the future in Australasia, In: Journal of genetic counseling30(1)pp. 55-60 Wiley

Current genetic counseling students will graduate into a workforce involving more opportunities, diversity, and uncertainty than any previous generation. Preparing the future genetic counseling workforce is a dynamic challenge, both for the profession and for educators. The dominance of the medical model in the state funded Australian healthcare system creates a power imbalance between doctors and other health professionals. As a result, professional regulation to protect the public from harm in line with the United States, the UK, and Canada only became mandatory in 2019. Professional regulation has the additional benefit of enhancing professional standing and autonomy, enabling genetic counselors to help shape the future of genetic health care in Australia and New Zealand. Within this rapidly evolving environment, we are establishing a new Masters' program and building a discipline of genetic counseling, working alongside other allied health professionals. Our program involves synchronous and asynchronous learning, greater accessibility, flexibility and, as we have learned in 2020, reduction in disruption during a global pandemic. In this program, we foreground the inherent knowledge, skills, and values of genetic counseling, shifting the focus from provision of genetic and genomic tests, to educating competent, person-centered, research enabled and culturally safe genetic counselors. As educators, we have a responsibility to prepare students to embrace the uncertainties, challenges, and potential of the genomic era, to seize the many possibilities that lie ahead, and to expand their thinking and vision. We ask our students to be courageous, to step into a deep exploration of their own identity, beliefs, understanding, and experiences of oppression, power, and privilege. We are pushing boundaries, and challenging ourselves and our students to remain always open to possibilities. Equipping students with open eyes and listening ears may be the single most important thing we can do to prepare the genetic counseling workforce of the future to provide the best possible care.

Phyllis Butow, Fabiola Müller, Christine E Napier, Nicci Bartley, Mandy L Ballinger, Barbara Biesecker, Ilona Juraskova, Bettina Meiser, Timothy E Schlub, David M Thomas, David Goldstein, Megan C Best, Christine June Jacobs (2021)Longitudinal patterns in fear of cancer progression in patients with rare, advanced cancers undergoing comprehensive tumour genomic profiling, In: Psycho-oncology (Chichester, England)30(11)pp. 1920-1929

Fear of cancer progression (FCP) impacts quality of life and is a prevalent unmet need in patients diagnosed with advanced cancer, particularly as treatment options are reduced. We aimed to identify longitudinal patterns in FCP over 6 months in patients with advanced cancer receiving comprehensive tumour genomic profiling (CTGP) results, and their correlates. Patients with pathologically confirmed metastatic disease (∼70% rare cancers) receiving or post their last line of standard therapy completed questionnaires at T0 (prior to CTGP), T1 (immediately post CTGP results) and T2 (2 months later). High stable (N = 52; 7.3%) and low/moderate stable (N = 56; 7.8%) FCP patterns over time typified the largest participant groups (N = 721). Those with an immediately actionable variant versus a non-actionable variant (p = 0.045), with higher FCP (p 

Lucy Bryant, Neira Sedlarevic, Peter Stubbs, Benjamin Bailey, Vincent Nguyen, Andrew Bluff, Diana Barnett, Matt Estela, Carolyn Hayes, Chris Jacobs, Ian Kneebone, Cherie Lucas, Poonam Mehta, Emma Power, Bronwyn Hemsley (2022)Collaborative co-design and evaluation of an immersive virtual reality application prototype for communication rehabilitation (DISCOVR prototype), In: Disability and rehabilitation: Assistive technologyahead-of-print(ahead-of-print)pp. 1-10 Taylor & Francis

Virtual reality (VR) lends itself to communication rehabilitation by creating safe, replicable, and authentic simulated environments in which users learn and practice communication skills. The aim of this research was to obtain the views of health professionals and technology specialists on the design characteristics and usability of a prototype VR application for communication rehabilitation. Nine professionals from different health and technology disciplines participated in an online focus group or individual online interview to evaluate the application and use of the VR prototype. Data sources were analysed using a content thematic analysis. Four main themes relating to VR design and implementation in rehabilitation were identified: (i) designing rehabilitation-focused virtual worlds; (ii) understanding and using VR hardware; (iii) making room for VR in rehabilitation and training; and (iv) implementing VR will not replace the health professional's role. Health professionals and technology specialists engaged in co-design while evaluating the VR prototype. They identified software features requiring careful consideration to ensure improved usability, client safety, and success in communication rehabilitation outcomes. Continuing inclusive co-design, engaging health professionals, clients with communication disability, and their families will be essential to creating useable VR applications and integrating these successfully into rehabilitation. Implications for rehabilitation Health and technology professionals, along with clients, are integral to the co-design of new VR technology applications. Design of VR applications needs to consider the client's communication, physical, cognitive, sensory, psychosocial, and emotional needs for greater usability of these programs. Realism and authenticity of interactions, characters, and environments are considered important factors to allow users to be fully immersed in virtual simulations to enhance rehabilitation.

Ranjit Manchanda, Oleg Blyuss, Faiza Gaba, Vladimir Sergeevich Gordeev, Chris Jacobs, Matthew Burnell, Carmen Gan, Rohan Taylor, Clare Turnbull, Rosa Legood, Alexey Zaikin, Antonis C Antoniou, Usha Menon, Ian Jacobs (2018)Current detection rates and time-to-detection of all identifiable BRCA carriers in the Greater London population, In: Journal of medical genetics55(8)538pp. 538-545

Background BRCA carrier identification offers opportunities for early diagnoses, targeted treatment and cancer prevention. We evaluate BRCA- carrier detection rates in general and Ashkenazi Jewish (AJ) populations across Greater London and estimate time-to-detection of all identifiable BRCA carriers.Methods BRCA carrier data from 1993 to 2014 were obtained from National Health Service genetic laboratories and compared with modelled predictions of BRCA prevalence from published literature and geographical data from UK Office for National Statistics. Proportion of BRCA carriers identified was estimated. Prediction models were developed to fit BRCA detection rate data. BRCA carrier identification rates were evaluated for an ‘Angelina Jolie effect’. Maps for four Greater London regions were constructed, and their relative BRCA detection rates were compared. Models developed were used to predict future time-to-identify all detectable BRCA carriers in AJ and general populations.ResultsUntil 2014, only 2.6% (3072/111 742 estimated) general population and 10.9% (548/4985 estimated) AJ population BRCA carriers have been identified in 16 696 608 (AJ=190 997) Greater London population. 57% general population and 54% AJ mutations were identified through cascade testing. Current detection rates mirror linear fit rather than parabolic model and will not identify all BRCA carriers. Addition of unselected ovarian/triple-negative breast cancer testing would take >250 years to identify all BRCA carriers. Doubling current detection rates can identify all ‘detectable’ BRCA carriers in the general population by year 2181, while parabolic and triple linear rates can identify ‘detectable’ BRCA carriers by 2084 and 2093, respectively. The linear fit model can identify ‘detectable’ AJ carriers by 2044. We did not find an Angelina Jolie effect on BRCA carrier detection rates. There was a significant difference in BRCA detection rates between geographical regions over time (P

Stephanie White, M. Gen Couns, Chris Jacobs, Jane Phillips (2020)Mainstreaming genetics and genomics: a systematic review of the barriers and facilitators for nurses and physicians in secondary and tertiary care, In: Genetics in medicine22(7)1149pp. 1149-1155 Elsevier

Purpose Genetic and genomic health information increasingly informs routine clinical care and treatment. This systematic review aimed to identify the barriers and facilitators to integrating genetics and genomics into nurses' and physicians' usual practice (mainstreaming). Methods A search of MEDLINE, EMBASE, CINAHL, and PsycINFO generated 7873 articles, of which 48 were included. Using narrative synthesis, barriers and facilitators were mapped to the Theoretical Domains Framework (TDF). Results Barriers were limitations to genetics knowledge and skill, low confidence initiating genetics discussions, lack of resources and guidelines, and concerns about discrimination and psychological harm. Facilitators were positive attitudes toward genetics, willingness to participate in discussions upon patient initiation, and intention to engage in genetics education. Conclusion Nurses and physicians are largely underprepared to integrate genetic and genomic health information into routine clinical care. Ethical, legal, and psychological concerns surrounding genetic information can lead to avoidance of genetics discussions. The knowledge-practice gap could limit patients' and families' access to vital genetic information. Building the capacity of the current and next generation of nurses and physicians to integrate genetics and genomics into usual clinical practice is essential if opportunities afforded by precision medicine are to be fully realized.

Clare Firth, Christine Jacobs, Margaret Evison, Gabriella Pichert, Louise Izatt, Myra S. Hunter (2011)Novel one-stop multidisciplinary follow-up clinic for BRCA1/2 carriers: patient satisfaction and decision making, In: Psycho-oncology (Chichester, England)20(12)1301pp. 1301-1308 Wiley

Objective: To evaluate patient' satisfaction and cancer risk management decision making, following attendance at a novel multidisciplinary one-stop follow-up clinic (MDOSC) for BRCA1/2 carriers. Patients and Methods: 172 patients attended the MDOSC over a 2-year period between 2006 and 2008. A total of 96 and 76 patients were seen in the first and second year, respectively. All patients who attended the MDOSC were sent a 17-item Satisfaction Questionnaire (SQ) designed to examine their views about the MDOSC, using rating scales and open questions after the first year. Patients were asked to comment on the most helpful aspects of the MDOSC and on how the service might be improved. Changes were made based on this feedback. During the second year, all patients were given the SQ with three questions about cancer risk management decision making on the day of the MDOSC. Results: In total, 132 (77%) patients responded and overall satisfaction was high with a mean of 8.94 (range 1-10). BRCA1/2 carriers were pleased to see a range of health care professionals on the same day, who they viewed gave consistent information, considered every aspect of care and addressed psychosocial needs. Following improvements, based on patients' feedback, satisfaction significantly increased in year 2. Furthermore, the MDOSC also helped patients to move forward with their cancer risk management decisions. Conclusions: BRCA1/2 carriers were highly satisfied with the MDOSC, which met their needs and helped them to make informed decisions regarding their cancer risk management. Copyright (C) 2010 John Wiley & Sons, Ltd.

Chris Jacobs, Belinda Rahman (2021)One size does not fit all: The case for targeted education in genetics and genomics for cancer nurses, In: European journal of cancer care30(4)13480pp. e13480-n/a Wiley
Elizabeth K Bancroft, Christine June Jacobs, Elizabeth C Page, Mark N Brook, Sarah Thomas, Natalie Taylor, Jennifer Pope, Jana McHugh, Ann-Britt Jones, Questa Karlsson, Susan Merson, Kai Ren Ong, Jonathan Hoffman, Camilla Huber, Lovise Maehle, Eli Marie Grindedal, Astrid Stormorken, D Gareth Evans, Jeanette Rothwell, Fiona Lalloo, Angela F Brady, Marion Bartlett, Katie Snape, Helen Hanson, Paul James, Joanne McKinley, Lyon Mascarenhas, Sapna Syngal, Chinedu Ukaegbu, Lucy Side, Tessy Thomas, Julian Barwell, Manuel R Teixeira, Louise Izatt, Mohnish Suri, Finlay A Macrae, Nicola Poplawski, Rakefet Chen-Shtoyerman, Munaza Ahmed, Hannah Musgrave, Nicola Nicolai, Lynn Greenhalgh, Carole Brewer, Nicholas Pachter, Allan D Spigelman, Ashraf Azzabi, Brian T Helfand, Dorothy Halliday, Saundra Buys, Teresa Ramon Y Cajal, Alan Donaldson, Kathleen A Cooney, Marion Harris, John McGrath, Rosemarie Davidson, Amy Taylor, Peter Cooke, Kathryn Myhill, Matthew Hogben, Neil K Aaronson, Audrey Ardern-Jones, Chris H Bangma, Elena Castro, David Dearnaley, Alexander Dias, Tim Dudderidge, Diana M Eccles, Kate Green, Jorunn Eyfjord, Alison Falconer, Christopher S Foster, Henrik Gronberg, Freddie C Hamdy, Oskar Johannsson, Vincent Khoo, Hans Lilja, Geoffrey J Lindeman, Jan Lubinski, Karol Axcrona, Christos Mikropoulos, Anita V Mitra, Clare Moynihan, Holly Ni Raghallaigh, Gad Rennert, Rebecca Collier, Judith Offman, Zsofia Kote-Jarai, Rosalind A Eeles (2021)A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective study, In: The lancet oncology22(11)1618pp. 1618-1631

Lynch syndrome is a rare familial cancer syndrome caused by pathogenic variants in the mismatch repair genes MLH1, MSH2, MSH6, or PMS2, that cause predisposition to various cancers, predominantly colorectal and endometrial cancer. Data are emerging that pathogenic variants in mismatch repair genes increase the risk of early-onset aggressive prostate cancer. The IMPACT study is prospectively assessing prostate-specific antigen (PSA) screening in men with germline mismatch repair pathogenic variants. Here, we report the usefulness of PSA screening, prostate cancer incidence, and tumour characteristics after the first screening round in men with and without these germline pathogenic variants. The IMPACT study is an international, prospective study. Men aged 40-69 years without a previous prostate cancer diagnosis and with a known germline pathogenic variant in the MLH1, MSH2, or MSH6 gene, and age-matched male controls who tested negative for a familial pathogenic variant in these genes were recruited from 34 genetic and urology clinics in eight countries, and underwent a baseline PSA screening. Men who had a PSA level higher than 3·0 ng/mL were offered a transrectal, ultrasound-guided, prostate biopsy and a histopathological analysis was done. All participants are undergoing a minimum of 5 years' annual screening. The primary endpoint was to determine the incidence, stage, and pathology of screening-detected prostate cancer in carriers of pathogenic variants compared with non-carrier controls. We used Fisher's exact test to compare the number of cases, cancer incidence, and positive predictive values of the PSA cutoff and biopsy between carriers and non-carriers and the differences between disease types (ie, cancer vs no cancer, clinically significant cancer vs no cancer). We assessed screening outcomes and tumour characteristics by pathogenic variant status. Here we present results from the first round of PSA screening in the IMPACT study. This study is registered with, NCT00261456, and is now closed to accrual. Between Sept 28, 2012, and March 1, 2020, 828 men were recruited (644 carriers of mismatch repair pathogenic variants [204 carriers of MLH1, 305 carriers of MSH2, and 135 carriers of MSH6] and 184 non-carrier controls [65 non-carriers of MLH1, 76 non-carriers of MSH2, and 43 non-carriers of MSH6]), and in order to boost the sample size for the non-carrier control groups, we randomly selected 134 non-carriers from the BRCA1 and BRCA2 cohort of the IMPACT study, who were included in all three non-carrier cohorts. Men were predominantly of European ancestry (899 [93%] of 953 with available data), with a mean age of 52·8 years (SD 8·3). Within the first screening round, 56 (6%) men had a PSA concentration of more than 3·0 ng/mL and 35 (4%) biopsies were done. The overall incidence of prostate cancer was 1·9% (18 of 962; 95% CI 1·1-2·9). The incidence among MSH2 carriers was 4·3% (13 of 305; 95% CI 2·3-7·2), MSH2 non-carrier controls was 0·5% (one of 210; 0·0-2·6), MSH6 carriers was 3·0% (four of 135; 0·8-7·4), and none were detected among the MLH1 carriers, MLH1 non-carrier controls, and MSH6 non-carrier controls. Prostate cancer incidence, using a PSA threshold of higher than 3·0 ng/mL, was higher in MSH2 carriers than in MSH2 non-carrier controls (4·3% vs 0·5%; p=0·011) and MSH6 carriers than MSH6 non-carrier controls (3·0% vs 0%; p=0·034). The overall positive predictive value of biopsy using a PSA threshold of 3·0 ng/mL was 51·4% (95% CI 34·0-68·6), and the overall positive predictive value of a PSA threshold of 3·0 ng/mL was 32·1% (20·3-46·0). After the first screening round, carriers of MSH2 and MSH6 pathogenic variants had a higher incidence of prostate cancer compared with age-matched non-carrier controls. These findings support the use of targeted PSA screening in these men to identify those with clinically significant prostate cancer. Further annual screening rounds will need to confirm these findings. Cancer Research UK, The Ronald and Rita McAulay Foundation, the National Institute for Health Research support to Biomedical Research Centres (The Institute of Cancer Research and Royal Marsden NHS Foundation Trust; Oxford; Manchester and the Cambridge Clinical Research Centre), Mr and Mrs Jack Baker, the Cancer Council of Tasmania, Cancer Australia, Prostate Cancer Foundation of Australia, Cancer Council of Victoria, Cancer Council of South Australia, the Victorian Cancer Agency, Cancer Australia, Prostate Cancer Foundation of Australia, Asociación Española Contra el Cáncer (AECC), the Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional (FEDER), the Institut Català de la Salut, Autonomous Government of Catalonia, Fundação para a Ciência e a Tecnologia, National Institutes of Health National Cancer Institute, Swedish Cancer Society, General Hospital in Malmö Foundation for Combating Cancer.

Dhivya Chandrasekaran, Usha Menon, Gareth Evans, Robin Crawford, Ertan Saridogan, Chris Jacobs, Marc Tischkowitz, Elly Brockbank, Jatinder Kalsi, Davor Jurkovic, Ranjit Manchanda (2015)Risk reducing salpingectomy and delayed oophorectomy in high risk women: views of cancer geneticists, genetic counsellors and gynaecological oncologists in the UK, In: Familial cancer14(4)pp. 521-530

Risk-reducing-salpingectomy and Delayed-Oophorectomy (RRSDO) is being proposed as a two-staged approach in place of RRSO to reduce the risks associated with premature menopause in high-risk women. We report on the acceptability/attitude of UK health professionals towards RRSDO. An anonymised web-based survey was sent to UK Cancer Genetics Group (CGG) and British Gynaecological Cancer Society (BGCS) members to assess attitudes towards RRSDO. Baseline characteristics were described using descriptive statistics. A Chi square test was used to compare categorical, Kendal-tau-b test for ordinal and Mann-Whitney test for continuous variables between two groups. 173/708 (24.4%) of invitees responded. 71% respondents (CGG = 57%/BGCS = 83%, p = 0.005) agreed with the tubal hypothesis for OC, 55% (CGG = 42%/BGCS = 66%, p = 0.003) had heard of RRSDO and 48% (CGG = 46%/BGCS = 50%) felt evidence was not currently strong enough for introduction into clinical practice. However, 60% respondents' (CGG = 48%/BGCS = 71%, p = 0.009) favoured offering RRSDO to high-risk women declining RRSO, 77% only supported RRSDO within a clinical trial (CGG = 78%/BGCS = 76%) and 81% (CGG = 76%/BGCS = 86%) advocated a UK-wide registry. Vasomotor symptoms (72%), impact on sexual function (63%), osteoporosis (59%), hormonal-therapy (55%) and subfertility (48%) related to premature menopause influenced their choice of RRSDO. Potential barriers to offering the two-stage procedure included lack of data on precise level of benefit (83%), increased surgical morbidity (79%), loss of breast cancer risk reduction associated with oophorectomy (68%), need for long-term follow-up (61%) and a proportion not undergoing DO (66%). There were variations in perception between BGCS/CGG members which are probably attributable to differences in clinical focus/expertise between these two groups. Despite concerns, there is reasonable support amongst UK clinicians to offering RRSDO to premenopausal high-risk women wishing to avoid RRSO, within a prospective clinical trial.

Megan Best, Ainsley J. Newson, Bettina Meiser, Ilona Juraskova, David Goldstein, Kathy Tucker, Mandy L. Ballinger, Dominique Hess, Timothy E. Schlub, Barbara Biesecker, Richard Vines, Kate Vines, David Thomas, Mary-Anne Young, Jacqueline Savard, Chris Jacobs, Phyllis Butow (2018)The PiGeOn project: protocol for a longitudinal study examining psychosocial, behavioural and ethical issues and outcomes in cancer tumour genomic profiling, In: BMC cancer18(1)389pp. 389-389 BioMed Central
David G. Cox, Christine June Jacobs, Jacques Simard, Daniel Sinnett, Yosr Hamdi, Penny Soucy, Manon Ouimet, Laure Barjhoux, Carole Verny-Pierre, Lesley McGuffog, Sue Healey, Csilla Szabo, Mark H. Greene, Phuong L. Mai, Irene L. Andrulis, Mads Thomassen, Anne-Marie Gerdes, Maria A. Caligo, Eitan Friedman, Yael Laitman, Bella Kaufman, Shani S. Paluch, Ake Borg, Per Karlsson, Marie Stenmark Askmalm, Gisela Barbany Bustinza, Katherine L. Nathanson, Susan M. Domchek, Timothy R. Rebbeck, Javier Benitez, Ute Hamann, Matti A. Rookus, Ans M. W. van den Ouweland, Margreet G. E. M. Ausems, Cora M. Aalfs, Christi J. van Asperen, Peter Devilee, Hans J. J. P. Gille, Susan Peock, Debra Frost, D. Gareth Evans, Ros Eeles, Louise Izatt, Julian Adlard, Joan Paterson, Jacqueline Eason, Andrew K. Godwin, Marie-Alice Remon, Virginie Moncoutier, Marion Gauthier-Villars, Christine Lasset, Sophie Giraud, Agnes Hardouin, Pascaline Berthet, Hagay Sobol, Francois Eisinger, Brigitte Bressac de Paillerets, Olivier Caron, Capucine Delnatte, David Goldgar, Alex Miron, Hilmi Ozcelik, Saundra Buys, Melissa C. Southey, Mary Beth Terry, Christian F. Singer, Anne-Catharina Dressler, Muy-Kheng Tea, Thomas V. O. Hansen, Oskar Johannsson, Marion Piedmonte, Gustavo C. Rodriguez, Jack B. Basil, Stephanie Blank, Amanda E. Toland, Marco Montagna, Claudine Isaacs, Ignacio Blanco, Simon A. Gayther, Kirsten B. Moysich, Rita K. Schmutzler, Barbara Wappenschmidt, Christoph Engel, Alfons Meindl, Nina Ditsch, Norbert Arnold, Dieter Niederacher, Christian Sutter, Dorothea Gadzicki, Britta Fiebig, Trinidad Caldes, Rachel Laframboise, Heli Nevanlinna, Xiaoqing Chen, Jonathan Beesley, Amanda B. Spurdle, Susan L. Neuhausen, Yuan C. Ding, Fergus J. Couch, Xianshu Wang, Paolo Peterlongo, Siranoush Manoukian, Loris Bernard, Paolo Radice, Douglas F. Easton, Georgia Chenevix-Trench, Antonis C. Antoniou, Dominique Stoppa-Lyonnet, Sylvie Mazoyer, Olga M. Sinilnikova (2011)Common variants of the BRCA1 wild-type allele modify the risk of breast cancer in BRCA1 mutation carriers, In: Human molecular genetics20(23)4732pp. 4732-4747 Oxford Univ Press

Mutations in the BRCA1 gene substantially increase a woman's lifetime risk of breast cancer. However, there is great variation in this increase in risk with several genetic and non-genetic modifiers identified. The BRCA1 protein plays a central role in DNA repair, a mechanism that is particularly instrumental in safeguarding cells against tumorigenesis. We hypothesized that polymorphisms that alter the expression and/or function of BRCA1 carried on the wild-type (non-mutated) copy of the BRCA1 gene would modify the risk of breast cancer in carriers of BRCA1 mutations. A total of 9874 BRCA1 mutation carriers were available in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) for haplotype analyses of BRCA1. Women carrying the rare allele of single nucleotide polymorphism rs16942 on the wild-type copy of BRCA1 were at decreased risk of breast cancer (hazard ratio 0.86, 95% confidence interval 0.77-0.95, P = 0.003). Promoter in vitro assays of the major BRCA1 haplotypes showed that common polymorphisms in the regulatory region alter its activity and that this effect may be attributed to the differential binding affinity of nuclear proteins. In conclusion, variants on the wild-type copy of BRCA1 modify risk of breast cancer among carriers of BRCA1 mutations, possibly by altering the efficiency of BRCA1 transcription.

Belinda Rahman, Alison McEwen, Jane L Phillips, Katherine Tucker, David Goldstein, Chris Jacobs (2022)Genetic and genomic learning needs of oncologists and oncology nurses in the era of precision medicine: a scoping review, In: Personalized medicine19(2)139pp. 139-153

Genetic and genomic data are increasingly guiding clinical care for cancer patients. To meet the growing demand for precision medicine, patient-facing oncology staff will be a part of leading the provision of genomic testing. A scoping review was undertaken to identify the range of genetic and genomic learning needs of oncologists and oncology nurses. Learning needs were reported relating to interpretation of genomic data, clinical decision-making, patient communication and counseling, and fundamentals of genetics and genomics. There was a lack of empirical research specific to oncology nurses and their learning needs in tumor sequencing. Our findings suggest that oncologists and oncology nurses need tailored support, education and training to improve their confidence and skills in adopting genomic testing into clinical practice.

R Manchanda, M Burnell, F Gaba, R Desai, J Wardle, S Gessler, L Side, S Sanderson, K Loggenberg, A F Brady, H Dorkins, Y Wallis, C Chapman, C Jacobs, R Legood, U Beller, I Tomlinson, U Menon, I Jacobs (2020)Randomised trial of population-based BRCA testing in Ashkenazi Jews: long-term outcomes, In: BJOG : an international journal of obstetrics and gynaecology127(3)pp. 364-375

Unselected population-based BRCA testing provides the opportunity to apply genomics on a population-scale to maximise primary prevention for breast-and-ovarian cancer. We compare long-term outcomes of population-based and family-history (FH)/clinical-criteria-based BRCA testing on psychological health and quality of life. Randomised controlled trial (RCT) (ISRCTN73338115) GCaPPS, with two-arms: (i) population-screening (PS); (ii) FH/clinical-criteria-based testing. North London Ashkenazi-Jewish (AJ) population. AJ women/men. Population-based RCT (1:1). Participants were recruited through self-referral, following pre-test genetic counselling from the North London AJ population. AJ women/men >18 years old; exclusion-criteria: prior BRCA testing or first-degree relatives of BRCA-carriers. Genetic testing for three Jewish BRCA founder-mutations: 185delAG (c.68_69delAG), 5382insC (c.5266dupC) and 6174delT (c.5946delT), for (i) all participants in PS arm; (ii) those fulfilling FH/clinical criteria in FH arm. Linear mixed models and appropriate contrast tests were used to analyse the impact of BRCA testing on psychological and quality-of-life outcomes over 3 years. Validated questionnaires (HADS/MICRA/HAI/SF12) used to analyse psychological wellbeing/quality-of-life outcomes at baseline/1-year/2-year/3-year follow up. In all, 1034 individuals (691 women, 343 men) were randomised to PS (n = 530) or FH (n = 504) arms. There was a statistically significant decrease in anxiety (P = 0.046) and total anxiety-&-depression scores (P = 0.0.012) in the PS arm compared with the FH arm over 3 years. No significant difference was observed between the FH and PS arms for depression, health-anxiety, distress, uncertainty, quality-of-life or experience scores associated with BRCA testing. Contrast tests showed a decrease in anxiety (P = 0.018), health-anxiety (P 

Stephanie White, Jane Phillips, Erin Turbitt, Chris Jacobs (2022)Views and experiences of palliative care clinicians in addressing genetics with individuals and families: a qualitative study, In: Supportive care in cancer30(2)1615pp. 1615-1624 Springer Nature

Purpose A proportion of people with palliative care needs unknowingly have a genetic predisposition to their disease, placing relatives at increased risk. As end-of-life nears, the opportunity to address genetics for the benefit of their family narrows. Clinicians face numerous barriers addressing genetic issues, but there is limited evidence from the palliative care clinician perspective. Our aims are to (1) explore the views and experiences of palliative care clinicians in addressing genetics with patients and their families and (2) generate suggested strategies that support integration of genetics into palliative care. Methods An interpretive descriptive qualitative study using semi-structured interviews with palliative care doctors and nurses (N = 14). Results Three themes were identified: (1) Harms and benefits of raising genetics: a delicate balancing act, (2) Navigating genetic responsibility within the scope of palliative care and (3) Overcoming practice barriers: a multipronged approach. Participants described balancing the benefits of addressing genetics in palliative care against potential harms. Responsibility to address genetic issues depends on perceptions of relevance and the scope of palliative care. Suggestions to overcome practice barriers included building genetic-palliative care relationships and multi-layered genetics education, developing clinical resources and increasing organisational support. Conclusions Integrating aspects of genetics is feasible, but must be balanced against potential harms and benefits. Palliative care clinicians were uncertain about their responsibility to navigate these complex issues to address genetics. There are opportunities to overcome barriers and tailor support to ensure people nearing end-of-life have a chance to address genetic issues for the benefit of their families.

C Loveday, Christine June Jacobs, A Garrett, P Law, S Hanks, E Poyastro-Pearson, J W Adlard, J Barwell, J Berg, A F Brady, C Brewer, C Chapman, J Cook, R Davidson, A Donaldson, F Douglas, L Greenhalgh, A Henderson, L Izatt, A Kumar, F Lalloo, Z Miedzybrodzka, P J Morrison, J Paterson, M Porteous, M T Rogers, L Walker, D Eccles, D G Evans, K Snape, H Hanson, R S Houlston, C Turnbull (2022)Analysis of rare disruptive germline mutations in 2135 enriched BRCA-negative breast cancers excludes additional high-impact susceptibility genes, In: Annals of oncology33(12)1318pp. 1318-1327

Breast cancer has a significant heritable basis, of which ∼60% remains unexplained. Testing for BRCA1/BRCA2 offers useful discrimination of breast cancer risk within families, and identification of additional breast cancer susceptibility genes could offer clinical utility. We included 2135 invasive breast cancer cases recruited via the Breast and Ovarian Cancer Susceptibility study, a retrospective UK study of familial breast cancer. female, BRCA-negative, white European ethnicity, and one of: (i) breast cancer family history, (ii) bilateral disease, (iii) young age of onset (80%) to detect a gene of BRCA1-like risk [odds ratio (OR) = 10.6] down to a population minor allele frequency of 4.6 × 10 (1 in 10 799, less than one-tenth that of BRCA1)and of PALB2-like risk (OR = 5.0) down to a population minor allele frequency of 2.8 × 10 (1 in 1779, less than half that of PALB2). Power was lower for identification of novel moderate penetrance genes (OR = 2-3) like CHEK2 and ATM. This is the largest case-control whole-exome analysis of enriched breast cancer published to date. Whilst additional breast cancer susceptibility genes likely exist, those of high penetrance are likely to be of very low mutational frequency. Contention exists regarding the clinical utility of such genes.

Alison Bish, Stephen Sutton, Christine Jacobs, Sara Levene, Amanda Ramirez, Shirley Hodgson (2002)No news is (not necessarily) good news: Impact of preliminary results for BRCA1 mutation searches, In: Genetics in medicine4(5)353pp. 353-358 Elsevier Inc

Purpose: Many women who have had breast or ovarian cancer who are undergoing tests for the presence of germline mutations in the BRCA1/2 genes will receive a result that is inconclusive. As this continuing uncertainty may have a detrimental effect on their psychological well-being and it is possible that such results will be misinterpreted as indicating that no mutation is present, studying their effect is important. Methods: Sixty-one women undergoing such tests completed questionnaires 2 weeks after their blood was taken and at 1 week and 6 months after receiving a preliminary “inconclusive” result, i.e., indicating that two thirds of the BRCA1 gene had been tested and no mutation had been found so far. Results: Perceived likelihood of having a mutation and perceptions of cancer risk significantly decreased after receipt of the interim result. There were no changes in levels of psychological distress and worry about cancer, in intentions to have mammograms, to carry out breast self-examination, or to have prophylactic surgery. Conclusions: The continuing uncertainty does not seem to have increased distress; however, it is possible that the inconclusive result is being interpreted as a “good news” result, in view of the fact that perceptions of risk decrease after receipt of the result.

Ashley Crook, Chris Jacobs, Toby Newton-John, Ebony Richardson, Alison McEwen (2021)Patient and Relative Experiences and Decision-making About Genetic Testing and Counseling for Familial ALS and FTD A Systematic Scoping Review, In: Alzheimer disease and associated disorders35(4)pp. 374-385 Lippincott Williams & Wilkins

Genetic testing and counseling is an emerging part of care for patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) and their families. This scoping review aimed to map patients' and relatives' experiences of genetic testing and counseling for familial ALS and FTD and the factors influencing their decision to proceed with testing or counseling. Informed by the Joanna Briggs Institute methodology, 5 databases were systematically searched. Thirty studies from 39 references were included. A descriptive numerical summary analysis and narrative synthesis was conducted. Mostly positive diagnostic testing experiences were reported, but issues arose due to progressive disease and discordant results. Predictive testing impacted at-risk relatives, regardless of the result received, and psychosocial sequelae ranged from relief to guilt, worry or contemplating suicide. Four reproductive testing experiences were reported. Personal, familial and practical factors, and the lived experience of disease, informed decision-making. Greater uncertainty and complexity may be faced in familial ALS/FTD than in other late-onset neurodegenerative diseases due to clinical and genetic heterogeneity, and testing limitations. Genetic counseling models of care should consider this difference to ensure that individuals with, or at risk of, ALS/FTD are effectively managed. Implications for research and practice are discussed.

Lucas A. Mitchell, Chris Jacobs, Alison McEwen (2023)(In)visibility of LGBTQIA plus people and relationships in healthcare: A scoping review, In: Patient education and counseling114107828 Elsevier

Objective: To identify and map research into the visibility of LGBTQIA+ people and their relationships in healthcare, with the view to inform future research and practice. Method: Five databases were systematically searched for published and grey literature. Primary research reporting on visibility of LGBTQIA+ people in healthcare was included. Two reviewers independently screened the studies until an acceptable level of agreement was reached. A narrative synthesis was conducted and findings mapped to a taxonomy of microaggressions involving three sub-categories: microinsults, microassaults and microinvalidations. Results: The microaggressions identified included Microinsults: 'Perception of health professionals' knowledge and comfort' and 'Disclosure'; Microassaults: 'Discrimination and stigma'; Microvalidations: 'Accessing and navigating through services', 'Encounters of assumptions and stereotypes', 'Validating identities and including relationships', and 'Reading the environment'. Conclusion: Despite growing societal acceptance, microaggressions still exist within healthcare. Groups within LGBTQIA+ communities have varying levels of visibility in research and healthcare based on the studies included. Practice implications: The limited visibility of LGBT and lack of visibility of QIA+ people and their relationships in healthcare highlight the need to include the views of all LGBTQIA+ communities in research, and to ensure health professionals and clinical services are equipped to address this (in)visibility gap.

Chris Jacobs, Gabriella Pichert, Jackie Harris, Kathy Tucker, Susan Michie (2017)Key messages for communicating information about BRCA1 and BRCA2 to women with breast or ovarian cancer: Consensus across health professionals and service users, In: Psycho-oncology (Chichester, England)26(11)pp. 1818-1824

Genetic testing of cancer predisposing genes will increasingly be needed in oncology clinics to target cancer treatment. This Delphi study aimed to identify areas of agreement and disagreement between genetics and oncology health professionals and service users about the key messages required by women with breast/ovarian cancer who undergo BRCA1/BRCA2 genetic testing and the optimal timing of communicating key messages. Participants were 16 expert health professionals specialising in oncology/genetics and 16 service users with breast/ovarian cancer and a pathogenic BRCA1/BRCA2 variant. Online questionnaires containing 53 inductively developed information messages were circulated to the groups separately. Participants rated each message as key/not key on a Likert scale and suggested additional messages. Questionnaires were modified according to the feedback and up to 3 rounds were circulated. Consensus was reached when there was ≥75% agreement. Thirty key messages were agreed by both groups with 7 of the key messages agreed by ≥95% of participants: dominant inheritance, the availability of predictive testing, the importance of pretest discussion, increased risk of breast and ovarian cancer, and the option of risk-reducing mastectomy and bilateral salpingo-oophorectomy. Both groups agreed that key messages should be communicated before genetic testing and once a pathogenic variant has been identified. There was a high level of agreement within and between the groups about the information requirements of women with breast/ovarian cancer about BRCA1/BRCA2. These key messages will be helpful in developing new approaches to the delivery of information as genetic testing becomes further integrated into mainstream oncology services.

Alison McEwen, Chris Jacobs (2021)Who we are, what we do, and how we add value: The role of the genetic counseling 'philosophy of practice' statement in a changing time, In: Journal of genetic counseling30(1)pp. 114-120 Wiley

As genetics and genomics are integrated into health care and non-genetic health professionals deliver aspects of genetic counseling, it is increasingly important for genetic counselors to be able to define who we are, what we do, and how we add value to client interactions, both on an individual and professional basis. In this paper, we argue that to understand ourselves as individual practitioners and as a profession, we each need to reflect on, write, and constantly review our own philosophy of practice. A philosophy of practice is a dynamic, personal, and reflective statement or narrative that captures the core ideas, values, and beliefs of the individual about their chosen profession, including concrete examples of what this involves in practice. Here, we consider the nature, purpose, and relevance of a philosophy of genetic counseling practice, drawing on examples from professions such as teaching and nursing, where the exercise of writing a philosophy of practice is more established. We demonstrate how and why we have introduced writing a philosophy of practice into our Master of Genetic Counseling program at University of Technology Sydney and consider the possibilities for introducing such practice into professional registration or certification processes. Finally, we offer our own philosophy of genetic counseling practice as an example. As the roles and scope of practice for genetic counselors expand and diversify, it is increasingly important to understand, own, and retain our core values and principles as individual practitioners and as a profession. Ensuring client-centered practice remains at the heart of genetic health care is vital. We encourage all genetic counselors to write, publish, and share their philosophy of practice, adding to our collective professional identity in this time of change and opportunity.

Ebony Richardson, Alison McEwen, Toby Newton-John, Karine Manera, Chris Jacobs (2021)The Core Outcome DEvelopment for Carrier Screening (CODECS) study: protocol for development of a core outcome set, In: Trials22(1)480pp. 480-480

Reproductive genetic carrier screening is a type of genetic testing available to those planning a pregnancy, or during their first trimester, to understand their risk of having a child with a severe genetic condition. There is a lack of consensus for 'what to measure' in studies on this intervention, leading to heterogeneity in choice of outcomes and methods of measurement. Such outcome heterogeneity has implications for the quality and comparability of these studies and has led to a lack of robust research evidence in the literature to inform policy and decision-making around the offer of this screening. As reproductive genetic carrier screening becomes increasingly accessible within the general population, it is timely to investigate the outcomes of this intervention. The development of a core outcome set is an established methodology to address issues with outcome heterogeneity in research. We aim to develop a core outcome set for reproductive genetic carrier screening to clarify and standardise outcomes for research and practice. In accordance with guidance from the COMET (Core Outcome Measures in Effectiveness Trials) Initiative, this study will consist of five steps: (i) a systematic review of quantitative studies, using narrative synthesis to identify previously reported outcomes, their definitions, and methods of measurement; (ii) a systematic review of qualitative studies using content analysis to identify excerpts related to patient experience and perspectives that can be interpreted as outcomes; (iii) semi-structured focus groups and interviews with patients who have undertaken reproductive genetic carrier screening to identify outcomes of importance to them; (iv) Delphi survey of key stakeholders, including patients, clinicians, and researchers, to refine and prioritise the list of outcomes generated from the previous steps; and (v) a virtual consensus meeting with a purposive sample of key stakeholders to finalise the core outcome set for reporting. This protocol outlines the core outcome set development process and its novel application in the setting of genetic testing. This core outcome set will support the standardisation of outcome reporting in reproductive carrier screening research and contribute to an evolving literature on outcomes to evaluate genetic testing and genetic counselling as health interventions. COMET CORE OUTCOME SET REGISTRATION: .

Ryan Pysar, Courtney K. Wallingford, Jackie Boyle, Scott B. Campbell, Lisa Eckstein, Rebekah McWhirter, Bronwyn Terrill, Chris Jacobs, Aideen M. McInerney-Leo (2021)Australian human research ethics committee members' confidence in reviewing genomic research applications, In: European journal of human genetics : EJHG29(12)pp. 1811-1818 Springer Nature

Human research ethics committees (HRECs) are evaluating increasing quantities of genomic research applications with complex ethical considerations. Genomic confidence is reportedly low amongst many non-genetics-experts; however, no studies have evaluated genomic confidence levels in HREC members specifically. This study used online surveys to explore genomic confidence levels, predictors of confidence, and genomics resource needs of members from 185 HRECs across Australia. Surveys were fully or partially completed by 145 members. All reported having postgraduate 94 (86%) and/or bachelor 15 (14%) degrees. Participants consisted mainly of researchers (n = 45, 33%) and lay members (n = 41, 30%), affiliated with either public health services (n = 73, 51%) or public universities (n = 31, 22%). Over half had served their HREC >= 3 years. Fifty (44%) reviewed genomic studies

Megan C. Best, Phyllis Butow, Jacqueline Savard, Chris Jacobs, Nicole Bartley, Grace Davies, Christine E. Napier, Mandy L. Ballinger, David M. Thomas, Barbara Biesecker, Katherine M. Tucker, Ilona Juraskova, Bettina Meiser, Timothy Schlub, Ainsley J. Newson (2022)Preferences for return of germline genome sequencing results for cancer patients and their genetic relatives in a research setting, In: European journal of human genetics : EJHG30(8)pp. 930-937 Springer Nature

Germline genome sequencing (GS) holds great promise for cancer prevention by identifying cancer risk and guiding prevention strategies, however research evidence is mixed regarding patient preferences for receiving GS results. The aim of this study was to discern preferences for return of results by cancer patients who have actually undergone GS. We conducted a mixed methods study with a cohort of cancer probands (n = 335) and their genetic relatives (n = 199) undergoing GS in a research setting. Both groups completed surveys when giving consent. A subset of participants (n = 40) completed semi-structured interviews. A significantly higher percentage of probands thought people would like to be informed about genetic conditions for which there is prevention or treatment that can change cancer risk compared to conditions for which there is no prevention or treatment (93% [311] versus 65% [216]; p < 0.001). Similar results were obtained for relatives (91% [180] versus 61% [121]; p < 0.001). Themes identified in the analysis of interviews were: (1) Recognised benefits of GS, (2) Balancing benefits with risks, (3) Uncertain results are perceived as unhelpful and (4) Competing obligations. While utility was an important discriminator in what was seen as valuable for this cohort, there was a variety of responses. In view of varied participant preferences regarding return of results, it is important to ensure patient understanding of test validity and identify individual choices at the time of consent to GS. The nature and value of the information, and a contextual understanding of researcher obligations should guide result return.

A. Jakubowska, C. Jacobs, D. Rozkrut, A. Antoniou, U. Hamann, R. J. Scott, L. McGuffog, S. Healy, O. M. Sinilnikova, G. Rennert, F. Lejbkowicz, A. Flugelman, I. L. Andrulis, G. Glendon, H. Ozcelik, M. Thomassen, M. Paligo, P. Aretini, J. Kantala, B. Aroer, A. Von Wachenfeldt, A. Liljegren, N. Loman, K. Herbst, U. Kristoffersson, R. Rosenquist, P. Karlsson, M. Stenmark-Askmalm, B. Melin, K. L. Nathanson, S. M. Domchek, T. Byrski, T. Huzarski, J. Gronwald, J. Menkiszak, C. Cybulski, P. Serrano, A. Osorio, T. R. Cajal, M. Tsitlaidou, J. Benitez, M. Gilbert, M. Rookus, C. M. Aalfs, I. Kluijt, J. L. Boessenkool-Pape, H. E. J. Meijers-Heijboer, J. C. Oosterwijk, C. J. van Asperen, M. J. Blok, M. R. Nelen, A. M. W. van den Ouweland, C. Seynaeve, R. B. van der Luijt, P. Devilee, D. F. Easton, S. Peock, D. Frost, R. Platte, S. D. Ellis, E. Fineberg, D. G. Evans, F. Lalloo, R. Eeles, J. Adlard, R. Davidson, D. Eccles, T. Cole, J. Cook, A. Godwin, B. Bove, D. Stoppa-Lyonnet, V. Caux-Moncoutier, M. Belotti, C. Tirapo, S. Mazoyer, L. Barjhoux, N. Boutry-Kryza, P. Pujol, I. Coupier, J-P Peyrat, P. Vennin, D. Muller, J-P Fricker, L. Venat-Bouvet, OTh Johannsson, C. Isaacs, R. Schmutzler, B. Wappenschmidt, A. Meindl, N. Arnold, R. Varon-Mateeva, D. Niederacher, C. Sutter, H. Deissler, S. Preisler-Adams, J. Simard, P. Soucy, F. Durocher, G. Chenevix-Trench, J. Beesley, X. Chen, T. Rebbeck, F. Couch, X. Wang, N. Lindor, Z. Fredericksen, V. S. Pankratz, P. Peterlongo, B. Bonanni, S. Fortuzzi, B. Peissel, C. Szabo, P. L. Mai, J. T. Loud, J. Lubinski (2012)Association of PHB 1630 C > T and MTHFR 677 C > T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: results from a multicenter study, In: British journal of cancer106(12)2016pp. 2016-2024 Springer Nature

BACKGROUND: The variable penetrance of breast cancer in BRCA1/2 mutation carriers suggests that other genetic or environmental factors modify breast cancer risk. Two genes of special interest are prohibitin (PHB) and methylene-tetrahydrofolate reductase (MTHFR), both of which are important either directly or indirectly in maintaining genomic integrity. METHODS: To evaluate the potential role of genetic variants within PHB and MTHFR in breast and ovarian cancer risk, 4102 BRCA1 and 2093 BRCA2 mutation carriers, and 6211 BRCA1 and 2902 BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA) were genotyped for the PHB 1630 C>T (rs6917) polymorphism and the MTHFR 677 C>T (rs1801133) polymorphism, respectively. RESULTS: There was no evidence of association between the PHB 1630 C>T and MTHFR 677 C>T polymorphisms with either disease for BRCA1 or BRCA2 mutation carriers when breast and ovarian cancer associations were evaluated separately. Analysis that evaluated associations for breast and ovarian cancer simultaneously showed some evidence that BRCA1 mutation carriers who had the rare homozygote genotype (TT) of the PHB 1630 C>T polymorphism were at increased risk of both breast and ovarian cancer (HR 1.50, 95% CI 1.10-2.04 and HR 2.16, 95% CI 1.24-3.76, respectively). However, there was no evidence of association under a multiplicative model for the effect of each minor allele. CONCLUSION: The PHB 1630TT genotype may modify breast and ovarian cancer risks in BRCA1 mutation carriers. This association need to be evaluated in larger series of BRCA1 mutation carriers. British Journal of Cancer (2012) 106, 2016-2024. doi:10.1038/bjc.2012.160 Published online 15 May 2012 (C) 2012 Cancer Research UK

Chris Jacobs, Stephanie White, Jane Phillips (2019)Genetics in palliative care: too much to ask?, In: International journal of palliative nursing25(5)212pp. 212-214 Mark Allen Group

People with an inherited condition who receive palliative care may be missing out on the opportunity to store a DNA sample for future use by their families and offspring. A DNA sample from a family member affected with an inherited condition can help at-risk relatives to access accurate risk assessment and, where relevant, enhanced surveillance and risk-reducing measures. As genetic and genomic testing becomes increasingly important in all aspects of healthcare, health professionals specialising in palliative care will be asked to communicate about family history risk and testing. This article highlights the importance of discussing genetics and genomics issues for people receiving palliative care, their families and the health professionals caring for them.

J. A. Smith, M. Stephenson, C. Jacobs, O. Quarrell (2013)Doing the right thing for one's children: deciding whether to take the genetic test for Huntington's disease as a moral dilemma, In: Clinical genetics83(5)pp. 417-421 Wiley

Smith JA, Stephenson M, Jacobs C, Quarrell O. Doing the right thing for one's children: deciding whether to take the genetic test for Huntington's disease as a moral dilemma. Clin Genet 2013: 83: 417-421. (C) John Wiley & Sons A/S. Published by Blackwell Publishing Ltd, 2013 This is a qualitative examination of candidates' decision-making in relation to the genetic test for Huntington's disease. Semi-structured interviews were conducted with nine participants who were asked about factors influencing their decision whether to take up predictive genetic testing. Transcripts of interviews were subjected to interpretative phenomenological analysis to elicit emergent themes. A key factor for participants was to do the right thing for their children. Interestingly, this factor presents a moral dilemma to participants and can direct them either towards or away from testing. This article offers a detailed examination of how participants think through this dilemma.

Danya F. Vears, Jackie Boyle, Chris Jacobs, Aideen McInerney-Leo, Ainsley J. Newson, (2023)Human Genetics Society of Australasia Position Statement: Genetic Carrier Testing for Recessive Conditions, In: Twin research and human genetics26(2)1832427423000154pp. 188-194 Cambridge University Press

This Position Statement provides guidelines to assist all health professionals who receive requests for carrier testing and laboratory staff conducting the tests. In this Statement, the term ‘carrier testing’ refers to genetic testing in an individual to determine whether they have inherited a pathogenic variant associated with an autosomal or X-linked recessive condition previously identified in a blood relative. Carrier testing recommendations: (1) Carrier testing should only be performed with the individual’s knowledge and consent; (2) An individual considering (for themselves, or on behalf of another) whether to have a carrier test should be supported to make an informed decision; (3) The mode of inheritance, the individual’s personal experience with the condition, and the healthcare setting in which the test is being performed should be considered when determining whether carrier testing should be offered by a genetic health professional. Regarding children and young people: Unless there is direct medical benefit in the immediate future, the default position should be to postpone carrier testing until the child or young person can be supported to make an informed decision. There may be some specific situations where it is appropriate to facilitate carrier testing in children and young people (see section in this article). In such cases, testing should only be offered with pre- and post-test genetic counseling in which genetic health professionals and parents/guardians should explore the rationale for testing and the interests of the child and the family.

Rosie O'Shea, Ashley Crook, Chris Jacobs, Maira Kentwell, Margaret Gleeson, Katherine M. Tucker, Heather Hampel, Alanna Kulchak Rahm, Natalie Taylor, Sarah Lewis, Nicole M. Rankin (2023)A mainstreaming oncogenomics model: improving the identification of Lynch syndrome, In: Frontiers in oncology131140135pp. 1140135-1140135 Frontiers Media Sa

Introduction"Mainstreaming" is a proposed strategy to integrate genomic testing into oncology. The aim of this paper is to develop a mainstreaming oncogenomics model by identifying health system interventions and implementation strategies for mainstreaming Lynch syndrome genomic testing. MethodsA rigorous theoretical approach inclusive of conducting a systematic review and qualitative and quantitative studies was undertaken using the Consolidated Framework for Implementation Research. Theory-informed implementation data were mapped to the Genomic Medicine Integrative Research framework to generate potential strategies. ResultsThe systematic review identified a lack of theory-guided health system interventions and evaluation for Lynch syndrome and other mainstreaming programs. The qualitative study phase included 22 participants from 12 health organizations. The quantitative Lynch syndrome survey included 198 responses: 26% and 66% from genetic and oncology health professionals, respectively. Studies identified the relative advantage and clinical utility of mainstreaming to improve genetic test access and to streamline care, and adaptation of current processes was recognized for results delivery and follow-up. Barriers identified included funding, infrastructure and resources, and the need for process and role delineation. The interventions to overcome barriers were as follows: embedded mainstream genetic counselors, electronic medical record genetic test ordering, results tracking, and mainstreaming education resources. Implementation evidence was connected through the Genomic Medicine Integrative Research framework resulting in a mainstreaming oncogenomics model. DiscussionThe proposed mainstreaming oncogenomics model acts as a complex intervention. It features an adaptable suite of implementation strategies to inform Lynch syndrome and other hereditary cancer service delivery. Implementation and evaluation of the model are required in future research.

Camelia Harrison, Nicci Bartley, Chris Jacobs, Megan Best, Sabina Vatter, Bettina Meiser, Mandy L. Ballinger, David M. Thomas, Phyllis Butow, (2023)Family communication and results disclosure after germline sequencing: A mixed methods study, In: Patient education and counseling114107800pp. 107800-107800 Elsevier

Objective: Research on family communication of germline genome sequencing (GS) results (versus of genetic results after targeted genetic testing) is still emerging, yet potentially complex results increase the importance of communicating risk to relatives. Promoting equity by ensuring patients have sufficient health literacy to interpret results is important in this context. This study aimed to identify cancer patients' perceived importance of result disclosure, predictors of perceptions, and perspectives on family communication. Methods: This explanatory-sequential, cross-sectional mixed-methods study involved participants (n = 246) completing a questionnaire and (n = 20) a semi-structured interview. Ordinal logistic regressions determined associations between potential predictors and perceived importance of result disclosure. Interview transcripts were analysed thematically using a constant-comparative approach. Results: More participants intended disclosing to nuclear (77.4%) than to extended family (42.7%). More than half (59.3%) felt results were family information; 62.7% believed it was important to disclose results to family members. Nuclear and extended family communication scores and education level were significantly positively associated with perceived importance of disclosure (p < 0.05). Six qualitative themes were identified: i) Re-sponsibility to inform, ii) Choice, iii) Autonomy, iv) Family Communication, v) Significance of results, and vi) Health professional role. Conclusion: Low health literacy and family conflict can complicate communication of GS results. Patients seek clear, interpretable information in a format they can easily communicate. Practice implications: Healthcare professionals can facilitate discussion of GS results by offering written infor-mation, encouraging disclosure, exploring existing family dynamics and communication patterns, and offering strategies to improve family communication. Centralised genetic communication offices and chatbots can also be helpful

Ebony Richardson, Alison McEwen, Toby Newton-John, Chris Jacobs (2023)Defining core outcomes of reproductive genetic carrier screening: A Delphi survey of Australian and New Zealand stakeholders, In: Prenatal diagnosis43(9)pp. 1150-1165 Wiley

ObjectiveUnderstanding the value, benefits and harms of health interventions is needed to inform best practice and ensure responsible implementation of new approaches to patient care. Such value is demonstrated through the assessment of outcomes; however, which outcomes are assessed is often highly varied across studies and can hinder the ability to draw robust conclusions. The Core Outcome Development for Carrier Screening study aims to understand the outcomes that can meaningfully capture the value of reproductive genetic carrier screening (RGCS). MethodThe authors report an iterative, two-round online Delphi survey of Australian and New Zealand stakeholders to determine the degree of consensus regarding the core outcomes of RGCS. Panellists ranked 83 outcomes according to their perceived importance on a nine-point Likert scale. Using the distribution of rankings, outcomes were grouped into tiers representative of their perceived level of importance and agreement between groups. ResultsThe top tier outcomes represent those agreed to be critically important for all future studies of RGCS to assess and were used to define a preliminary core outcome set encompassing the domains (1) primary laboratory outcomes, (2) pregnancy outcomes, (3) resource use and, (4) perceived utility of RGCS. ConclusionThese findings can guide the selection of meaningful outcomes in studies aiming to demonstrate the value of RGCS. A future international consensus process will expand on these findings and guide the inclusion of diverse perspectives across the range of settings in which RGCS is offered.

Ashley Crook, Chris Jacobs, Toby Newton-John, Rosie O'Shea, Alison McEwen (2022)Genetic counseling and testing practices for late-onset neurodegenerative disease: a systematic review, In: Journal of neurology269(2)pp. 676-692 Springer Nature

Objective To understand contemporary genetic counseling and testing practices for late-onset neurodegenerative diseases (LONDs), and identify whether practices address the internationally accepted goals of genetic counseling: interpretation, counseling, education, and support. Methods Four databases were systematically searched for articles published from 2009 to 2020. Peer-reviewed research articles in English that reported research and clinical genetic counseling and testing practices for LONDs were included. A narrative synthesis was conducted to describe different practices and map genetic counseling activities to the goals. Risk of bias was assessed using the Qualsyst tool. The protocol was registered with PROSPERO (CRD42019121421). Results Sixty-one studies from 68 papers were included. Most papers focused on predictive testing (58/68) and Huntington's disease (41/68). There was variation between papers in study design, study population, outcomes, interventions, and settings. Although there were commonalities, novel and inconsistent genetic counseling practices were identified. Eighteen papers addressed all four goals of genetic counseling. Conclusion Contemporary genetic counseling and testing practices for LONDs are varied and informed by regional differences and the presence of different health providers. A flexible, multidisciplinary, client- and family-centered care continues to emerge. As genetic testing becomes a routine part of care for patients (and their relatives), health providers must balance their limited time and resources with ensuring clients are safely and effectively counseled, and all four genetic counseling goals are addressed. Areas of further research include diagnostic and reproductive genetic counseling/testing practices, evaluations of novel approaches to care, and the role and use of different health providers in practice.

Caroline Dancyger, Mel Wiseman, Chris Jacobs, Jonathan A. Smith, Melissa Wallace, Susan Michie (2011)Communicating BRCA1/2 genetic test results within the family: A qualitative analysis, In: Psychology & health26(8)1018pp. 1018-1035 Taylor & Francis

Genetic testing for BRCA1/2 mutations associated with hereditary breast and ovarian cancer reveals significant risk information about one's chances of developing cancer. It is important to study communication processes in families where members are undergoing genetic testing because the information received is crucial not just to the individual concerned but also to other members of the biological family. This study investigates family communication of BRCA1/2 test results from both the informants' and recipients' perspectives. A total of 10 female patients and 22 of their relatives were interviewed. Patients' and their relatives described feelings of responsibility for sharing genetic information within the family to enable others to reduce their risks of developing cancer. However, there were limits to an individuals' responsibility once key family members had been informed, who then had to take responsibility for continuing dissemination of information. Whilst there was an implicit responsibility to inform the family of a mutation, information was edited or withheld in the best interest of relatives, dependent upon their perceived emotional readiness, resilience and current life stage and circumstances. The pre-existing family culture and the impact previous cancer diagnoses had upon the family also influenced the process of communication. Findings are discussed in relation to extant literature and implications for clinical practice are considered.

Rosie O'Shea, Natalie Taylor, Ashley Crook, Chris Jacobs, Yoon Jung Kang, Sarah Lewis, Nicole M. Rankin (2021)Health system interventions to integrate genetic testing in routine oncology services: A systematic review, In: PloS one16(5)0250379pp. e0250379-e0250379 Public Library Science

Background Integration of genetic testing into routine oncology care could improve access to testing. This systematic review investigated interventions and the tailored implementation strategies aimed at increasing access to genetic counselling and testing and identifying hereditary cancer in oncology. Methods The search strategy results were reported using the PRISMA statement and four electronic databases were searched. Eligible studies included routine genetic testing for breast and ovarian cancer or uptake after universal tumour screening for colorectal or endometrial cancer. The titles and abstracts were reviewed and the full text articles screened for eligibility. Data extraction was preformed using a designed template and study appraisal was assessed using an adapted Newcastle Ottawa Scale. Extracted data were mapped to Proctor's et al outcomes and the Consolidated Framework for Implementation Research and qualitatively synthesised. Results Twenty-seven studies, published up to May 2020, met the inclusion criteria. Twenty-five studies ranged from poor (72%), fair to good (28%) quality. Most interventions identified were complex (multiple components) such as; patient or health professional education, interdisciplinary practice and a documentation or system change. Forty-eight percent of studies with complex interventions demonstrated on average a 35% increase in access to genetic counselling and a 15% increase in testing completion. Mapping of study outcomes showed that 70% and 32% of the studies aligned with either the service and client or the implementation level outcome and 96% to the process or inner setting domains of the Consolidated Framework for Implementation Research. Conclusion Existing evidence suggests that complex interventions have a potentially positive effect towards genetic counselling and testing completion rates in oncology services. Studies of sound methodological quality that explore a greater breadth of pre and post implementation outcomes and informed by theory are needed. Such research could inform future service delivery models for the integration of genetics into oncology services.

Tatiane Yanes, Vaishnavi Nathan, Courtney Wallingford, Rhonda Faragher, Karen Nankervis, Chris Jacobs, Maria Vassos, Fran Boyle, Annemaree Carroll, Simon Smith, Aideen McInerney-Leo (2023)Australasian genetic counselors' attitudes toward disability and prenatal testing: Findings from a cross‐sectional survey, In: Journal of genetic counseling

Abstract Diagnostic genetic testing and non‐invasive prenatal testing (NIPT) for conditions associated with disability are becoming increasingly available to consumers. This genetic information can be used in the disability setting to inform factors such as prognosis, management, and reproductive decision‐making. Genetic counselors (GCs) play an important role in the provision of genetic testing and NIPT, and their attitudes toward disability can influence how genetic information is communicated and shape patients' responses. This study aimed to evaluate and describe Australasian GCs' experience with and attitudes toward disabilities to identify potential biases and training needs. A cross‐sectional survey was distributed to 400 GCs registered with the Human Genetics Society of Australasia. Of the 106 respondents (participation rate: 26%), a significantly greater proportion were more comfortable interacting with individuals with physical disability as compared to intellectual disability ( p < 0.001). GCs with personal experiences with disabilities reported significantly greater comfort interacting with people with intellectual disability than those without experience ( p = 0.012). Qualitative analysis revealed discomfort was less reflective of bias than inexperience and apprehension about communicating disrespectfully. GCs believed people with disabilities experience discrimination and that having a disability could make a person stronger, wiser, and more motivated. Most GCs viewed prenatal testing for disabilities positively as it allowed for decisions regarding continuing the pregnancy and/or provided opportunity to prepare. Challenges identified for prenatal counseling included negative societal attitudes and the low visibility of disability. GCs felt that ‘personal beliefs’ was the primary factor influencing the decision to terminate a pregnancy affected by disability. These findings highlight important education and training needs for GCs to improve preparedness and comfort when communicating with people with a disability.

Courtney K. Wallingford, Hannah Kovilpillai, Chris Jacobs, Erin Turbitt, Clare A. Primiero, Mary-Anne Young, Deanna G. Brockman, H. Peter Soyer, Aideen M. McInerney-Leo, Tatiane Yanes (2023)Models of communication for polygenic scores and associated psychosocial and behavioral effects on recipients: A systematic review, In: Genetics in medicine25(1)pp. 1-11 Elsevier

Purpose: This study aimed to systematically review current models for communicating poly genic scores (PGS) and psycho-behavioral outcomes of receiving PGSs.Methods: Original research on communicating PGSs and reporting on psycho-behavioral outcomes was included. Search terms were applied to 5 databases and were limited by date (2009-2021).Results: In total, 28 articles, representing 17 studies in several disease settings were identified. There was limited consistency in PGS communication and evaluation/reporting of outcomes. Most studies (n = 14) presented risk in multiple ways (ie, numerically, verbally, and/or visually). Three studies provided personalized lifestyle advice and additional resources. Only 1 of 17 studies reported using behavior change theory to inform their PGS intervention. A total of 8 studies found no evidence of long-term negative psychosocial effects up to 12 months post result. Of 14 studies reporting on behavior, 9 found at least 1 favorable change after PGS receipt. When stratified by risk, 7 out of 9 studies found high PGS was associated with favorable changes including lifestyle, medication, and screening. Low-risk PGS was not associated with maladaptive behaviors (n = 4).Conclusion: PGS has the potential to benefit health behavior. High variability among studies emphasizes the need for developing standardized guidelines for communicating PGSs and evaluating psycho-behavioral outcomes. Our findings call for development of best communication practices and evidence-based interventions informed by behavior change theories.(c) 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.

Ebony Richardson, Alison McEwen, Toby Newton-John, Ashley Crook, Chris Jacobs (2022)Outcomes of Importance to Patients in Reproductive Genetic Carrier Screening: A Qualitative Study to Inform a Core Outcome Set, In: Journal of personalized medicine12(8)1310 Mdpi

There is significant heterogeneity in the outcomes assessed across studies of reproductive genetic carrier screening (RGCS). Only a small number of studies have measured patient-reported outcomes or included patients in the selection of outcomes that are meaningful to them. This study was a cross-sectional, qualitative study of 15 patient participants conducted to inform a core outcome set. A core outcome set is an approach to facilitate standardisation in outcome reporting, allowing direct comparison of outcomes across studies to enhance understanding of impacts and potential harms. The aim of this study was to incorporate the patient perspective in the development of a core outcome set by eliciting a detailed understanding of outcomes of importance to patients. Data were collected via online, semi-structured interviews using a novel method informed by co-design and the nominal group technique. Data were analysed using reflexive thematic analysis. Outcomes elicited from patient stakeholder interviews highlighted several under-explored areas for future research. This includes the role of grief and loss in increased risk couples, the role of empowerment in conceptualising the utility of RGCS, the impact of societal context and barriers that contribute to negative experiences, and the role of genetic counselling in ensuring that information needs are met and informed choice facilitated as RGCS becomes increasingly routine. Future research should focus on incorporating outcomes that accurately reflect patient needs and experience.

Caroline Dancyger, Jonathan A. Smith, Chris Jacobs, Melissa Wallace, Susan Michie (2010)Comparing family members' motivations and attitudes towards genetic testing for hereditary breast and ovarian cancer: a qualitative analysis, In: European journal of human genetics : EJHG18(12)pp. 1289-1295 Springer Nature

Genetic testing for hereditary breast and ovarian cancer reveals significant risk information regarding one's chances of developing cancer that has potential implications for patients and their families. This study reports on the motivations and attitudes of index patients and their relatives towards genetic testing for hereditary breast and ovarian cancer. In total, 10 female index patients and 20 of their relatives were interviewed regarding their experiences of communicating genetic information within their families, and their motivations and attitudes towards genetic testing. The analysis found two types of 'family groups': groups strongly committed to genetic testing and groups uncertain about testing. Within committed family groups, index patients and their relatives felt obliged to be tested for others, leading some relatives to be tested without having fully thought through their decision or the implications of knowing their mutation status. These family groups also described considerations in relation to the value of testing for themselves. In family groups uncertain about testing, relatives had not attended for predictive testing, had postponed decision making until some point in the future or had expressed ambivalence about the value of testing for themselves. Results suggest the value of explicitly acknowledging motivations for genetic testing within the context of family obligations, relationships and communication, and the possible value of involving family members in genetic counselling and decision making from a family's first contact with genetic services. European Journal of Human Genetics (2010) 18, 1289-1295; doi: 10.1038/ejhg.2010.114; published online 21 July 2010

Matthew Burnell, Faiza Gaba, Monika Sobocan, Rakshit Desai, Saskia Sanderson, Kelly Loggenberg, Sue Gessler, Lucy Side, Angela F Brady, Huw Dorkins, Yvonne Wallis, Chris Jacobs, Rosa Legood, Uziel Beller, Ian Tomlinson, Jane Wardle, Usha Menon, Ian Jacobs, Ranjit Manchanda (2022)Randomised trial of population-based BRCA testing in Ashkenazi Jews: long-term secondary lifestyle behavioural outcomes, In: BJOG : an international journal of obstetrics and gynaecology129(12)pp. 1970-1980

Ashkenazi-Jewish (AJ) population-based BRCA testing is acceptable, cost-effective and amplifies primary prevention for breast & ovarian cancer. However, data describing lifestyle impact are lacking. We report long-term results of population-based BRCA testing on lifestyle behaviour and cancer risk perception. Two-arm randomised controlled trials (ISRCTN73338115, GCaPPS): (a) population-screening (PS); (b) family history (FH)/clinical criteria testing. North London AJ-population. AJ women/men >18 years. prior BRCA testing or first-degree relatives of BRCA-carriers. Participants were recruited through self-referral. All participants received informed pre-test genetic counselling. The intervention included genetic testing for three AJ BRCA-mutations: 185delAG(c.68_69delAG), 5382insC(c.5266dupC) and 6174delT(c.5946delT). This was undertaken for all participants in the PS arm and participants fulfilling FH/clinical criteria in the FH arm. Patients filled out customised/validated questionnaires at baseline/1-year/2-year/3-year follow-ups. Generalised linear-mixed models adjusted for covariates and appropriate contrast tests were used for between-group/within-group analysis of lifestyle and behavioural outcomes along with evaluating factors associated with these outcomes. Outcomes are adjusted for multiple testing (Bonferroni method), with P 

Fergus J. Couch, Chris Jacobs, Mia M. Gaudet, Antonis C. Antoniou, Susan J. Ramus, Karoline B. Kuchenbaecker, Penny Soucy, Jonathan Beesley, Xiaoqing Chen, Xianshu Wang, Tomas Kirchhoff, Lesley McGuffog, Daniel Barrowdale, Andrew Lee, Sue Healey, Olga M. Sinilnikova, Irene L. Andrulis, Hilmi Ozcelik, Anna Marie Mulligan, Mads Thomassen, Anne-Marie Gerdes, Uffe Birk Jensen, Anne-Bine Skytte, Torben A. Kruse, Maria A. Caligo, Anna von Wachenfeldt, Gisela Barbany-Bustinza, Niklas Loman, Maria Soller, Hans Ehrencrona, Per Karlsson, Katherine L. Nathanson, Timothy R. Rebbeck, Susan M. Domchek, Ania Jakubowska, Jan Lubinski, Katarzyna Jaworska, Katarzyna Durda, Elzbieta Zlowocka, Tomasz Huzarski, Tomasz Byrski, Jacek Gronwald, Cezary Cybulski, Bohdan Gorski, Ana Osorio, Mercedes Duran, Maria Isabel Tejada, Javier Benitez, Ute Hamann, Frans B. L. Hogervorst, Theo A. van Os, Flora E. van Leeuwen, Hanne E. J. Meijers-Heijboer, Juul Wijnen, Marinus J. Blok, Marleen Kets, Maartje J. Hooning, Rogier A. Oldenburg, Margreet G. E. M. Ausems, Susan Peock, Debra Frost, Steve D. Ellis, Radka Platte, Elena Fineberg, D. Gareth Evans, Rosalind A. Eeles, Julian Adlard, Rosemarie Davidson, Diana M. Eccles, Trevor Cole, Jackie Cook, Joan Paterson, Carole Brewer, Fiona Douglas, Shirley V. Hodgson, Patrick J. Morrison, Lisa Walker, Mary E. Porteous, M. John Kennedy, Lucy E. Side, Betsy Bove, Andrew K. Godwin, Dominique Stoppa-Lyonnet, Marion Fassy-Colcombet, Laurent Castera, Francois Cornelis, Sylvie Mazoyer, Melanie Leone, Nadia Boutry-Kryza, Brigitte Bressac-de Paillerets, Olivier Caron, Pascal Pujol, Isabelle Coupier, Capucine Delnatte, Linda Akloul, Henry T. Lynch, Carrie L. Snyder, Saundra S. Buys, Mary B. Daly, MaryBeth Terry, Wendy K. Chung, Esther M. John, Alexander Miron, Melissa C. Southey, John L. Hopper, David E. Goldgar, Christian F. Singer, Christine Rappaport, Muy-Kheng M. Tea, Anneliese Fink-Retter, Thomas V. O. Hansen, Finn C. Nielsen, Adalgeir Arason, Joseph Vijai, Sohela Shah, Kara Sarrel, Mark E. Robson, Marion Piedmonte, Kelly Phillips, Jack Basil, Wendy S. Rubinstein, John Boggess, Katie Wakeley, Amanda Ewart-Toland, Marco Montagna, Simona Agata, Evgeny N. Imyanitov, Claudine Isaacs, Ramunas Janavicius, Conxi Lazaro, Ignacio Blanco, Lidia Feliubadalo, Joan Brunet, Simon A. Gayther, Paul P. D. Pharoah, Kunle O. Odunsi, Beth Y. Karlan, Christine S. Walsh, Edith Olah, Soo Hwang Teo, Patricia A. Ganz, Mary S. Beattie, Elizabeth J. van Rensburg, Cecelia M. Dorfling, Orland Diez, Ava Kwong, Rita K. Schmutzler, Barbara Wappenschmidt, Christoph Engel, Alfons Meindl, Nina Ditsch, Norbert Arnold, Simone Heidemann, Dieter Niederacher, Sabine Preisler-Adams, Dorothea Gadzicki, Raymonda Varon-Mateeva, Helmut Deissler, Andrea Gehrig, Christian Sutter, Karin Kast, Britta Fiebig, Wolfram Heinritz, Trinidad Caldes, Miguel de la Hoya, Taru A. Muranen, Heli Nevanlinna, Marcd Tischkowitz, Amanda B. Spurdle, Susan L. Neuhausen, Yuan Chun Ding, Noralane M. Lindor, Zachary Fredericksen, V. Shane Pankratz, Paolo Peterlongo, Siranoush Manoukian, Bernard Peissel, Daniela Zaffaroni, Monica Barile, Loris Bernard, Alessandra Viel, Giuseppe Giannini, Liliana Varesco, Paolo Radice, Mark H. Greene, Phuong L. Mai, Douglas F. Easton, Georgia Chenevix-Trench, Kenneth Offit, Jacques Simard (2012)Common Variants at the 19p13.1 and ZNF365 Loci Are Associated with ER Subtypes of Breast Cancer and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers, In: Cancer epidemiology, biomarkers & prevention21(4)645pp. 645-657 Amer Assoc Cancer Research

Background: Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for these variants in mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Methods: Genotyping data for 12,599 BRCA1 and 7,132 BRCA2 mutation carriers from 40 studies were combined. Results: We confirmed associations between rs8170 at 19p13.1 and breast cancer risk for BRCA1 mutation carriers [HR, 1.17; 95% confidence interval (CI), 1.07-1.27; P = 7.42 x 10(-4)] and between rs16917302 at ZNF365 (HR, 0.84; 95% CI, 0.73-0.97; P = 0.017) but not rs311499 at 20q13.3 (HR, 1.11; 95% CI, 0.94-1.31; P = 0.22) and breast cancer risk for BRCA2 mutation carriers. Analyses based on tumor histopathology showed that 19p13 variants were predominantly associated with estrogen receptor (ER)-negative breast cancer for both BRCA1 and BRCA2 mutation carriers, whereas rs16917302 at ZNF365 was mainly associated with ER-positive breast cancer for both BRCA1 and BRCA2 mutation carriers. We also found for the first time that rs67397200 at 19p13.1 was associated with an increased risk of ovarian cancer for BRCA1 (HR, 1.16; 95% CI, 1.05-1.29; P = 3.8 x 10(-4)) and BRCA2 mutation carriers (HR, 1.30; 95% CI, 1.10-1.52; P = 1.8 x 10(-3)). Conclusions: 19p13.1 and ZNF365 are susceptibility loci for ovarian cancer and ER subtypes of breast cancer among BRCA1 and BRCA2 mutation carriers. Impact: These findings can lead to an improved understanding of tumor development and may prove useful for breast and ovarian cancer risk prediction for BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev; 21(4); 645-57. (C) 2012 AACR.

Erin Turbitt, Chris Jacobs, Alison McEwen (2023)Special Issue: "Genetic Counseling and Genetic Testing in Precision Medicine", In: Journal of personalized medicine13(8)1192 Mdpi
Megan C Best, Nicole Bartley, Chris Jacobs, Ilona Juraskova, David Goldstein, Ainsley J Newson, Jacqueline Savard, Bettina Meiser, Mandy Ballinger, Christine Napier, David Thomas, Barbara Biesecker, Phyllis Butow, (2019)Patient perspectives on molecular tumor profiling: "Why wouldn't you?", In: BMC cancer19(1)753pp. 753-753

This study explored the attitudes of patients with advanced cancer towards MTP and return of results, prior to undergoing genomic testing within a research program. Participants were recruited as part of the longitudinal PiGeOn (Psychosocial Issues in Genomics in Oncology) study involving patients with advanced/metastatic solid cancer who had exhausted therapeutic options and who were offered MTP in order to identify cognate therapies. Twenty patients, selected by purposive sampling, were interviewed around the time they gave consent to MTP. Interviews were audio recorded, transcribed and analysed using thematic analysis. Themes identified in the transcripts were cross-validated via qualitative responses to the PiGeOn study survey (n = 569; 63%). All interviewed participants gave consent to MTP without reservation. Three themes were identified and further supported via the survey responses: (1) Obvious agreement to participate, primarily because of desire for new treatments and altruism. (2) The black box - while participant knowledge of genomics was generally poor, faith in their oncologists and the scientific process encouraged them to proceed with testing; and (3) Survival is the priority - receiving treatment to prolong life was the priority for all participants, and other issues such as identification of a germline variant were generally seen as ancillary. Having advanced cancer seemed to abrogate any potential concerns about MTP. Participants valued the research for varied reasons, but this was secondary to their priority to survive. While no negative attitudes toward MTP emerged, limitations in understanding of genomics were evident.

D. Reisel, M. Burnell, L. Side, K. Loggenberg, S. Gessler, R. Desai, S. Sanderson, A. F. Brady, H. Dorkins, Y. Wallis, C. Jacobs, R. Legood, U. Beller, Tomlinson, J. Wardle, U. Menon, Jacobs, R. Manchanda (2022)Jewish cultural and religious factors and uptake of population-based BRCA testing across denominations: a cohort study, In: BJOG : an international journal of obstetrics and gynaecology129(6)959pp. 959-968 Wiley

Objective To evaluate the association of Jewish cultural and religious identity and denominational affiliation with interest in, intention to undertake and uptake of population-based BRCA (Breast Cancer Gene)-testing. Design Cohort-study set within recruitment to GCaPPS-trial (ISRCTN73338115). Setting London Ashkenazi-Jewish (AJ) population. Population or sample AJ men and women, >18 years. Methods Participants were self-referred, and attended recruitment clinics (clusters) for pre-test counselling. Subsequently consenting individuals underwent BRCA testing. Participants self-identified to one Jewish denomination: Conservative/Liberal/Reform/Traditional/Orthodox/Unaffiliated. Validated scales measured Jewish Cultural-Identity (JI) and Jewish Religious-identity (JR). Four-item Likert-scales analysed initial 'interest' and 'intention to test' pre-counselling. Item-Response-Theory and graded-response models, modelled responses to JI and JR scales. Ordered/multinomial logistic regression modelling evaluated association of JI-scale, JR-scale and Jewish Denominational affiliation on interest, intention and uptake of BRCA testing. Main outcome measures Interest, intention, uptake of BRCA testing. Results In all, 935 AJ women/men of mean age = 53.8 (S.D = 15.02) years, received pre-test education and counselling through 256 recruitment clinic clusters (median cluster size = 3). Denominational affiliations included Conservative/Masorti = 91 (10.2%); Liberal = 82 (9.2%), Reform = 135 (15.1%), Traditional = 212 (23.7%), Orthodox = 239 (26.7%); and Unaffiliated/Non-practising = 135 (15.1%). Overall BRCA testing uptake was 88%. Pre-counselling, 96% expressed interest and 60% intention to test. JI and JR scores were highest for Orthodox, followed by Conservative/Masorti, Traditional, Reform, Liberal and Unaffiliated Jewish denominations. Regression modelling showed no significant association between overall Jewish Cultural or Religious Identity with either interest, intention or uptake of BRCA testing. Interest, intention and uptake of BRCA testing was not significantly associated with denominational affiliation. Conclusions Jewish religious/cultural identity and denominational affiliation do not appear to influence interest, intention or uptake of population-based BRCA testing. BRCA testing was robust across all Jewish denominations. Tweetable abstract Jewish cultural/religious factors do not affect BRCA testing, with robust uptake seen across all denominational affiliations.

G. Pichert, C. Jacobs, I. Jacobs, U. Menon, R. Manchanda, M. Johnson, H. Hamed, C. Firth, M. Evison, A. Tutt, L. de Silva, C. Langman, L. Izatt (2010)Novel one-stop multidisciplinary follow-up clinic significantly improves cancer risk management in BRCA1/2 carriers, In: Familial cancer9(3)313pp. 313-319 Springer Nature

The purpose of this study is to measure the impact of a multidisciplinary one-stop follow-up clinic (MDOSC) on breast and ovarian surveillance, risk reducing surgery and enrolment in clinical trials in BRCA1/2 carriers. All BRCA1/2 carriers in our region were invited and chose which specialists to see in our MDOSC offering best practice using clinical protocols based on national guidelines and published data. Uptake was evaluated over 24 months recording numbers of individuals undergoing breast and ovarian surveillance, risk reducing surgery, newly diagnosed cancers, their method of detection and participation in clinical trials. 172 (60%) of invited BRCA1/2 carriers chose to attend the MDOSC. Breast surveillance was initiated in 88% and screening frequency altered in 14% of women to comply with national guidelines. Risk reducing salpingo-oophorectomy was chosen by 47% of women and an additional 39% were considering it. The rate of failure to remove fallopian tubes fell from 15 to 3% of procedures (P < 0.01) and peritoneal washings and serial sectioning of tubes and ovaries rose from 25% and 14% before, to 67% (P < 0.001) and 63% (P < 0.001) procedures, respectively, after initiation of our MDOSC. 24% of women considered and 18% decided to undergo risk reducing mastectomy during the follow-up period. Participation in clinical trials increased significantly from 51 to 229 enrolments (P < 0.001). Our novel MDOSC designed to devise an individually tailored cancer risk management strategy had a high uptake amongst our BRCA1/2 carriers. Attendance resulted in improved breast and ovarian cancer risk management.

Grace Dowling, Jane Tiller, Aideen McInerney-Leo, Andrea Belcher, Casey Haining, Kristine Barlow-Stewart, Tiffany Boughtwood, Penny Gleeson, Martin B Delatycki, Ingrid Winship, Margaret Otlowski, Chris Jacobs, Louise Keogh, Paul Lacaze (2022)Health professionals' views and experiences of the Australian moratorium on genetic testing and life insurance: A qualitative study, In: European journal of human genetics : EJHG30(11)pp. 1262-1268

Australian life insurance companies can legally use genetic test results in underwriting, which can lead to genetic discrimination. In 2019, the Financial Services Council (Australian life insurance industry governing body) introduced a partial moratorium restricting the use of genetic testing in underwriting policies ≤ $500,000 (active 2019-2024). Health professionals (HPs), especially clinical geneticists and genetic counsellors, often discuss the implications of genetic testing with patients, and provide critical insights into the effectiveness of the moratorium. Using a sequential explanatory mixed methods design, we interviewed 23 Australian HPs, who regularly discuss genetic testing with patients and had previously completed an online survey about genetic testing and life insurance. Interviews explored views and experiences about the moratorium, and regulation, in greater depth. Interview transcripts were analysed using thematic analysis. Two key themes emerged from views expressed by HPs during interviews (about matters reported to or observed by them): 1) benefits of the moratorium, and 2) concerns about the moratorium. While HPs reported that the moratorium reassures some consumers, concerns include industry self-regulation, uncertainty created by the temporary time period, and the inadequacy of the moratorium's financial limits for patients' financial needs. Although a minority of HPs felt the current industry self-regulated moratorium is an adequate solution to genetic discrimination, the vast majority (19/23) expressed concern with industry self-regulation and most felt government regulation is required to adequately protect consumers. HPs in Australia are concerned about the adequacy of the FSC moratorium with regards to consumer protections, and suggest government regulation is required.

Stephanie White, Erin Turbitt, Jane L. Phillips, Chris Jacobs (2023)Approaching discussions about genetics with palliative patients and their families: a qualitative exploration with genetic health professionals, In: European journal of human genetics : EJHG31(8)pp. 945-952 Springer Nature

Genetic information can provide clinical benefits to families of palliative patients. However, integration of genetics into mainstream medicine has not focused on palliative populations. We explored the views and experiences of genetic health professionals in addressing genetics with palliative patients, and their families. We conducted an interpretive descriptive qualitative study with genetic counsellors and clinical geneticists using interviews and focus groups. Findings were generated using reflexive thematic analysis. Three themes were identified: (1) Focusing on the benefit to the family, (2) The discomfort of addressing genetics near end-of-life and (3) "It's always on the back-burner": Challenges to getting genetics on the palliative care agenda. Participants discussed the familial benefit of genetics in palliative care alongside the challenges when patients are near end-of-life. They perceived genetics as low priority for palliative care due to misunderstandings related to the value of genetic information. Acknowledging the challenges in the palliative care context, genetic health professionals want improved service leadership and awareness of the familial benefits of palliative genetic testing. Strong leadership to support genetic health professionals in addressing these barriers is needed for the benefits of genetic information to be realised.

Amelia K. Smit, Nicci Bartley, Megan C. Best, Christine E. Napier, Phyllis Butow, Ainsley J. Newson, Kathy Tucker, Mandy L. Ballinger, David M. Thomas, Chris Jacobs, Bettina Meiser, David Goldstein, Jacqueline Savard, Ilona Juraskova, (2021)Family communication about genomic sequencing: A qualitative study with cancer patients and relatives, In: Patient education and counseling104(5)pp. 944-952 Elsevier

Objective: This study explored family communication about undertaking genomic sequencing, and intentions to communicate pertinent heritable results to family members. Methods: Semi-structured interviews were conducted with cancer patients (n = 53) and their relatives (n = 20) who underwent germline genome sequencing or molecular tumor testing. Interviews were audio-recorded, transcribed and analyzed using thematic analysis. Results: Key themes relevant to family communication about undertaking sequencing included: perceiving family member interest, delaying discussion until results were received, having shared capacity to understand and cope, and having open communication in the family. Intended communication subsequent to receiving results was affected by: disease severity, risk management options, degree of closeness in the family, sense of responsibility, and potential adverse impacts on family. Resource and support needs varied based on the complexity of test results, health professionals' availability, and disease severity. Unique subthemes were identified for specific subgroups. Conclusion: Current findings support the need to assess the impact and resource needs specific to each clinical application of genomic sequencing. Practice implications: Increasingly sophisticated and complex clinical genomic sequencing warrants development of family-centered interventions and resources to facilitate preference-sensitive communication about genomic sequencing, including disseminating relevant information to family members. (c) 2020 Elsevier B.V. All rights reserved.

Ashley Crook, Chris Jacobs, Toby Newton-John, Alison McEwen (2022)Genetic counseling and diagnostic genetic testing for familial amyotrophic lateral sclerosis and/or frontotemporal dementia: A qualitative study of client experiences, In: Journal of genetic counseling31(5)pp. 1206-1218

Genetic counseling and diagnostic genetic testing is part of the multidisciplinary care of people with amyotrophic lateral sclerosis (ALS, commonly called motor neurone disease, MND) and frontotemporal dementia (FTD). We explored client experiences of genetic counseling and diagnostic testing to inform the care of future families. Semi‐structured interviews with individuals with ALS/MND/FTD or their relatives were conducted. The study was designed to include a wide variety of participants with varying disease status and abilities. Genetic counseling and diagnostic testing experiences were explored using interpretive description methodology. Bioecological theory was used as the framework for the reflexive thematic analysis. Eighteen individuals with ALS/MND/FTD or their relatives from 13 Australian families participated. Three themes were identified: sharing knowledge, (un)supportive care, and ‘circumstance is everything’. Consistent with bioecological theory, one’s genetic counseling experience was informed by individual circumstances, time, and proximal factors. These informed the level of information and support required in the genetic counseling process. Although some client circumstances cannot be changed, efforts could be made to enhance genetic counseling experiences by improving interactions between the client and their care team. Some clients may benefit from further discussions regarding the familial implications of genetic testing, and greater support with family communication. Clients’ needs were derived from the data and will contribute to genetic counseling consensus guidelines.

Ashley Crook, Chris Jacobs, Toby Newton-John, Alison McEwen (2022)Toward genetic counseling practice standards for diagnostic testing in amyotrophic lateral sclerosis and frontotemporal dementia, In: Amyotrophic lateral sclerosis and frontotemporal degeneration23(7-8)pp. 562-574 Taylor & Francis

Objective: Genetic counseling and diagnostic genetic testing are considered part of the multidisciplinary care of individuals with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We aimed to investigate the ideal components of genetic counseling for ALS/FTD diagnostic testing amongst various stakeholders using an online, modified Delphi survey. Methods: Experts in genetic counseling and testing for ALS/FTD were purposively then snowball recruited and included genetic health professionals, health professionals outside of genetics and consumer experts (patients, relatives, and staff representatives from ALS/FTD support organizations). First-round items were informed by two systematic literature reviews and qualitative interviews with patients and families who had experienced diagnostic testing. Analysis of each round informed the development of the subsequent round and the final results. Results: Forty-six experts participated in the study, 95.65% completed both rounds. After round one, items were updated based on participant responses and were presented again for consensus in round two. After round two, a high level of consensus (≥80% agreement) was achieved on 16 items covering various topics related to genetic counseling service delivery, before and after diagnostic testing is facilitated. Conclusions: Genetic counseling for individuals with ALS/FTD and their families should include the provision of client-centered counseling, education and support throughout. The items developed are adaptable to varied healthcare settings and may inform a standard of genetic counseling practice for health professionals who facilitate testing and counseling discussions. This area of work is timely, given demand for testing is likely to increase as more genotype-driven clinical trials become available.

Antonis C Antoniou, Christine June Jacobs, Christiana Kartsonaki, Olga M Sinilnikova, Penny Soucy, Lesley McGuffog, Sue Healey, Andrew Lee, Paolo Peterlongo, Siranoush Manoukian, Bernard Peissel, Daniela Zaffaroni, Elisa Cattaneo, Monica Barile, Valeria Pensotti, Barbara Pasini, Riccardo Dolcetti, Giuseppe Giannini, Anna Laura Putignano, Liliana Varesco, Phuong L Mai, Paolo Radice, Mark H Greene, Irene L Andrulis, Gord Glendon, Hilmi Ozcelik, Mads Thomassen, Anne-Marie Gerdes, Torben A Kruse, Uffe Birk Jensen, Dorthe G Crüger, Maria A Caligo, Yael Laitman, Roni Milgrom, Bella Kaufman, Shani Paluch-Shimon, Eitan Friedman, Niklas Loman, Katja Harbst, Annika Lindblom, Brita Arver, Hans Ehrencrona, Beatrice Melin, Katherine L Nathanson, Susan M Domchek, Timothy Rebbeck, Ania Jakubowska, Jan Lubinski, Jacek Gronwald, Tomasz Huzarski, Tomasz Byrski (2011)Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, In: Human molecular genetics

Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 × 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 × 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.

D. Gareth R. Evans, Julian Barwell, Diana M. Eccles, Amanda Collins, Louise Izatt, Chris Jacobs, Alan Donaldson, Angela F. Brady, Andrew Cuthbert, Rachel Harrison, Sue Thomas, Anthony Howell, Zosia Miedzybrodzka, Alex Murray, (2014)The Angelina Jolie effect: how high celebrity profile can have a major impact on provision of cancer related services, In: Breast cancer research : BCR16(5)442pp. 442-442 Springer Nature

Introduction: It is frequent for news items to lead to a short lived temporary increase in interest in a particular health related service, however it is rare for this to have a long lasting effect. In 2013, in the UK in particular, there has been unprecedented publicity in hereditary breast cancer, with Angelina Jolie's decision to have genetic testing for the BRCA1 gene and subsequently undergo risk reducing mastectomy (RRM), and a pre-release of the NICE guidelines on familial breast cancer in January and their final release on 26th June. The release of NICE guidelines created a lot of publicity over the potential for use of chemoprevention using tamoxifen or raloxifene. However, the longest lasting news story was the release of details of film actress Angelina Jolie's genetic test and surgery. Methods: To assess the potential effects of the 'Angelina Jolie' effect, referral data specific to breast cancer family history was obtained from around the UK for the years 2012 and 2013. A consortium of over 30 breast cancer family history clinics that have contributed to two research studies on early breast surveillance were asked to participate as well as 10 genetics centres. Monthly referrals to each service were collated and increases from 2012 to 2013 assessed. Results: Data from 12 family history clinics and 9 regional genetics services showed a rise in referrals from May 2013 onwards. Referrals were nearly 2.5 fold in June and July 2013 from 1,981 (2012) to 4,847 (2013) and remained at around two-fold to October 2013. Demand for BRCA1/2 testing almost doubled and there were also many more enquiries for risk reducing mastectomy. Internal review shows that there was no increase in inappropriate referrals. Conclusions: The Angelina Jolie effect has been long lasting and global, and appears to have increased referrals to centres appropriately.

Rebecca Daly, Kate Hetherington, Emily Hazell, Bethany R Wadling, Vanessa Tyrrell, Katherine M Tucker, Glenn M Marshall, David S Ziegler, Loretta M S Lau, Toby N Trahair, Tracey A O'Brien, Kiri Collins, Andrew J Gifford, Michelle Haber, Mark Pinese, David Malkin, Mark J Cowley, Jonathan Karpelowsky, Donna Drew, Chris Jacobs, Claire E Wakefield (2023)Precision Medicine Is Changing the Roles of Healthcare Professionals, Scientists, and Research Staff: Learnings from a Childhood Cancer Precision Medicine Trial, In: Journal of personalized medicine13(7)1033

Precision medicine programs aim to utilize novel technologies to identify personalized treatments for children with cancer. Delivering these programs requires interdisciplinary efforts, yet the many groups involved are understudied. This study explored the experiences of a broad range of professionals delivering Australia's first precision medicine trial for children with poor-prognosis cancer: the PRecISion Medicine for Children with Cancer (PRISM) national clinical trial of the Zero Childhood Cancer Program. We conducted semi-structured interviews with 85 PRISM professionals from eight professional groups, including oncologists, surgeons, clinical research associates, scientists, genetic professionals, pathologists, animal care technicians, and nurses. We analyzed interviews thematically. Professionals shared that precision medicine can add complexity to their role and result in less certain outcomes for families. Although many participants described experiencing a greater emotional impact from their work, most expressed very positive views about the impact of precision medicine on their profession and its future potential. Most reported navigating precision medicine without formal training. Each group described unique challenges involved in adapting to precision medicine in their profession. Addressing training gaps and meeting the specific needs of many professional groups involved in precision medicine will be essential to ensure the successful implementation of standard care.

Tara Darmody, Sue 'Brian, Kris Rogers, Mark Onslow, Chris Jacobs, Alison McEwen, Robyn Lowe, Ann Packman, Ross Menzies (2022)Stuttering, family history and counselling: A contemporary database, In: Journal of fluency disorders73105925pp. 105925-105925 Elsevier

Background: Information about genetic influence is useful to when counselling parents or caregivers who have infants and children at risk for stuttering. Yet, the most comprehensive family aggregate database to inform that counselling is nearly four decades old (Andrews et al., 1983). Consequently, the present study was designed to provide a contemporary exploration of the relationship between stuttering and family history.Methods: Data were sourced from the Australian Stuttering Research Centre, comprising 739 participants who presented for assessment, treatment, or investigation of stuttering. Reported family history data were acquired from pedigrees collected during assessment. We sought to establish the relation of the following variables to family history of stuttering: incidence, proband sex, parent sex, stuttering severity, age, reported age of stuttering onset, and impact of stuttering. Data were analysed with chi-square tests for independence, logistic and linear regression models. Results: Results were broadly consistent with existing data, but the following findings were novel. Males and females who stutter have the same increased odds of having a father who stutters relative to a mother who stutters. Males had later stuttering onset than females, with genetic involvement in this effect. There was a greater impact of stuttering for females than males with a family history of stuttering.Conclusion: These findings have clinical applications. Speech-language pathologists may have infant or child clients known to them who are at risk of beginning to stutter. Information from the present study can be applied to counselling parents or caregivers of such children about stuttering and family history.

D Ellis, J Greenman, S Hodgson, S McCall, F Lalloo, J Cameron, L Izatt, G Scott, C Jacobs, S Watts, W Chorley, C Perrett, K Macdermot, S Mohammed, G Evans, C G Mathew (2000)Low prevalence of germline BRCA1 mutations in early onset breast cancer without a family history, In: Journal of medical genetics37(10)pp. 792-794
Mia M. Gaudet, Chris Jacobs, Karoline B. Kuchenbaecker, Joseph Vijai, Robert J. Klein, Tomas Kirchhoff, Lesley McGuffog, Daniel Barrowdale, Alison M. Dunning, Andrew Lee, Joe Dennis, Sue Healey, Ed Dicks, Penny Soucy, Olgam Sinilnikova, Vernon S. Pankratz, Xianshu Wang, Ronald C. Eldridge, Daniel C. Tessier, Daniel Vincent, Francois Bacot, Frans B. L. Hogervorst, Susan Peock, Dominique Stoppa-Lyonnet, Paolo Peterlongo, Rita K. Schmutzler, Katherine L. Nathanson, Marion Piedmonte, Christian F. Singer, Mads Thomassen, Thomas V. O. Hansen, Susan L. Neuhausen, Ignacio Blanco, Mark H. Greene, Judith Garber, Jeffrey N. Weitzel, Irene L. Andrulis, David E. Goldgar, Emma D'Andrea, Trinidad Caldes, Heli Nevanlinna, Ana Osorio, Elizabeth J. van Rensburg, Adalgeir Arason, Gad Rennert, Ans M. W. van den Ouweland, Annemarie H. van der Hout, Carolien M. Kets, Cora M. Aalfs, Juul T. Wijnen, Margreet G. E. M. Ausems, Debra Frost, Steve Ellis, Elena Fineberg, Radka Platte, D. Gareth Evans, Julian Adlard, Marc Tischkowitz, Mary E. Porteous, Francesca Damiola, Lisa Golmard, Laure Barjhoux, Michel Longy, Muriel Belotti, Sandra Fert Ferrer, Sylvie Mazoyer, Amanda B. Spurdle, Siranoush Manoukian, Monica Barile, Maurizio Genuardi, Norbert Arnold, Alfons Meindl, Christian Sutter, Barbara Wappenschmidt, Susan M. Domchek, Georg Pfeiler, Eitan Friedman, Uffe Birk Jensen, Mark Robson, Sohela Shah, Conxi Lazaro, Phuong L. Mai, Javier Benitez, Melissa C. Southey, Marjanka K. Schmidt, Peter A. Fasching, Julian Peto, Manjeet K. Humphreys, Qin Wang, Kyriaki Michailidou, Elinor J. Sawyer, Barbara Burwinkel, Pascal Guenel, Stig E. Bojesen, Roger L. Milne, Hermann Brenner, Magdalena Lochmann, Kristiina Aittomaki, Thilo Doerk, Sara Margolin, Arto Mannermaa, Diether Lambrechts, Jenny Chang-Claude, Paolo Radice, Graham G. Giles, Christopher A. Haiman, Robert Winqvist, Peter Devillee, Montserrat Garcia-Closas, Nils Schoof, Maartje J. Hooning, Angela Cox, Paul D. P. Pharoah, Anna Jakubowska, Nick Orr, Anna Gonzalez-Neira, Guillermo Pita, M. Rosario Alonso, Per Hall, Fergus J. Couch, Jacques Simard, David Altshuler, Douglas F. Easton, Georgia Chenevix-Trench, Antonis C. Antoniou, Kenneth Offit (2013)Identification of a BRCA2-Specific Modifier Locus at 6p24 Related to Breast Cancer Risk, In: PLoS genetics9(3)1003173pp. e1003173-e1003173 Public Library Science

Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9 x 10(-8)). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer.

Megan C. Best, Phyllis Butow, Chris Jacobs, Jacqueline Savard, Barbara Biesecker, Mandy L. Ballinger, Nicci Bartley, Grace Davies, Christine E. Napier, Amelia K. Smit, David M. Thomas, Ainsley J. Newson, (2020)Who should access germline genome sequencing? A mixed methods study of patient views, In: Clinical genetics97(2)pp. 329-337 Blackwell Publishing Ltd

Implementation of any new medical test, including germline genome sequencing (GS) to inform cancer risk, should take place only when a test is effective, ethically justifiable and acceptable to a population. Little empirical evidence exists on patient views regarding GS for cancer risk. The aim of this study was to elicit opinions on who should be offered GS and who should pay for it. Participants with a probable genetic basis for their cancer (n = 335) and blood relatives (n = 199) were recruited to undergo GS and invited to complete questionnaires at baseline. A subset (n = 40) also participated in qualitative interviews about their views regarding access to GS to detect cancer risk. Our response rate was 92% for questionnaires and 100% for interviews. Participants expressed high enthusiasm overall for access to GS for those with a family history of cancer and anyone who requested testing, but enthusiasm was lower for universal access, if opting out was possible and finances not an issue. Rationales for these views reflected maximising the sound use of resources. Challenges to introducing community screening via GS to limit cancer burden were raised, including the current limits of science and individual ability to cope with uncertain results. Participants undergoing GS supported cancer risk testing for those with a family history of cancer but were concerned about the challenges of designing and implementing a population‐based GS cancer‐screening program.

Chris Jacobs, Erin Turbitt, Alison McEwen, Lou Atkins (2022)Australasian Genetic Counselors' Perceptions of Their Role in Supporting Clients' Behavior Change, In: Journal of personalized medicine13(1)30 Mdpi

Genetic testing does not always change health behavior. Effective behavior change requires a theory-driven coordinated set of activities (behavior change techniques). Genetic counselors are ideally positioned to facilitate behavior change. We aimed to explore genetic counselors' perceptions of their role in supporting clients' behavior change to inform the design of an intervention. Recruitment was via a professional organization and genetics services. Data were collected from 26 genetic counselors via qualitative focus groups/interview. Transcripts were analyzed using thematic analysis and mapped to the COM-B model. We identified three behaviors genetic counselors wanted clients to change: attend appointments, access information, and share information with family members. Strategies for changing clients' behavior included: assessing needs and capabilities, providing information and support, enabling and monitoring behavior change. Barriers included lack of behavior change skills and knowledge, lack of time, and beliefs about ownership of healthcare, directiveness of behavior change, and scope of practice. Equipping genetic counselors to deliver behavior change requires (i) education in behavior change theory and behavior change techniques, (ii) integration of capability, opportunity and motivation assessment into existing practice, and (iii) development of evidence-based strategies using behavior change tools to focus discussions and promote clients' agency to change their behavior.

Jane M Tiller, Nicole E Cousens, Rajneesh Kaur, Simone Rowley, Yi-An Ko, Sakshi Mahale, Agnes Bankier, Bettina Meiser, Kristine Barlow-Stewart, Leslie Burnett, Chris Jacobs, Paul James, Alison Trainer, Suzanne Neil, Ian G Campbell, Lesley Andrews, Martin Delatycki (2023)Population-based BRCA1/2 testing programmes are highly acceptable in the Jewish community: results of the JeneScreen Study, In: Journal of medical genetics60(3)265pp. 265-273 BMJ Publishing Group Ltd

BackgroundAshkenazi Jewish (AJ) people have a higher incidence of BRCA1/2 pathogenic variants (PVs) than unselected populations. Three BRCA-Jewish founder mutations (B-JFMs) comprise >90% of BRCA1/2 PVs in AJ people. Personal/family cancer history-based testing misses ≥50% of people with B-JFM.MethodsWe compared two population-based B-JFM screening programmes in Australia—using (1) an online tool (Sydney) and (2) in-person group sessions (Melbourne).ResultsOf 2167 Jewish people tested (Sydney n=594; Melbourne n=1573), 1.3% (n=28) have a B-JFM, only 2 of whom had a significant cancer family history (Manchester score ≥12). Pretest anxiety scores were normal (mean 9.9±3.5 (6–24)), with no significant post-result change (9.5±3.3). Decisional regret (mean 7.4±13.0 (0–100)), test-related distress (mean 0.8+/2.2 (0–30)) and positive experiences (reverse-scored) (mean 3.4±4.5 (1–20)) scores were low, with no significant differences between Sydney and Melbourne participants. Post-education knowledge was good overall (mean 11.8/15 (±2.9)) and significantly higher in Melbourne than Sydney. Post-result knowledge was the same (mean 11.7 (±2.4) vs 11.2 (±2.4)). Participants with a B-JFM had higher post-result anxiety and test-related distress and lower positive experiences, than those without a B-JFM, but scores were within the normal range. Family cancer history did not significantly affect knowledge or anxiety, or pretest perception of B-JFM or cancer risks. Most participants (93%) were satisfied/very satisfied with the programme.ConclusionBoth B-JFM screening programmes are highly acceptable to Australian Jewish communities. The programme enabled identification of several individuals who were previously unaware they have a B-JFM, many of whom would have been ineligible for current criteria-based testing in Australia.

Chris Jacobs, Gabriella Pichert (2016)Genetic Testing for Rare Cancer: The Wider Issues, In: G Pichert, C Jacobs (eds.), Rare Hereditary Cancerspp. 213-226 Springer Nature

Identification of a potential genetic susceptibility to cancer and confirmation of a pathogenic gene mutation raises a number of challenging issues for the patient with cancer, their relatives and the health professionals caring for them. The specific risks and management issues associated with rare cancer types have been addressed in the earlier chapters. This chapter considers the wider issues involved in genetic counselling and genetic testing for a genetic susceptibility to cancer for patients, families and health professionals. The first part of the chapter will present the issues raised by the current practice in genetic counselling and genetic testing for cancer susceptibility. The second part of the chapter will address some of the issues raised by the advances in genetic testing technology and the future opportunities provided by personalised medicine and targeted cancer therapy. Facilitating these developments requires closer integration of genomics into mainstream cancer care, challenging the existing paradigm of genetic medicine, adding additional layers of complexity to the risk assessment and management of cancer and presenting wider issues for patients, families, health professionals and clinical services.

Nicole E Cousens, Jane Tiller, Bettina Meiser, Kristine Barlow-Stewart, Simone Rowley, Yi-An Ko, Sakshi Mahale, Ian G Campbell, Rajneesh Kaur, Agnes Bankier, Leslie Burnett, Chris Jacobs, Paul A James, Alison Trainer, Suzanne Neil, Martin B Delatycki, Lesley Andrews (2021)Evaluation of two population screening programmes for BRCA1/2 founder mutations in the Australian Jewish community: a protocol paper, In: BMJ open11(6)e041186pp. e041186-e041186

IntroductionPeople of Ashkenazi Jewish (AJ) ancestry are more likely than unselected populations to have a BRCA1/2 pathogenic variant, which cause a significantly increased risk of breast, ovarian and prostate cancer. Three specific BRCA1/2 pathogenic variants, referred to as BRCA-Jewish founder mutations (B-JFM), account for >90% of BRCA1/2 pathogenic variants in people of AJ ancestry. Current practice of identifying eligible individuals for BRCA testing based on personal and/or family history has been shown to miss at least 50% of people who have one of these variants. Here we describe the protocol of the JeneScreen study—a study established to develop and evaluate two different population-based B-JFM screening programmes, offered to people of Jewish ancestry in Sydney and Melbourne, Australia.Methods and analysisTo rmeasure the acceptability of population-based B-JFM screening in Australia, two screening programmes using different methodologies have been developed. The Sydney JeneScreen programme provides information and obtains informed consent by way of an online tool. The Melbourne JeneScreen programme does this by way of community sessions attended in person. Participants complete questionnaires to measure clinical and psychosocial outcomes at baseline, and for those who have testing, 2 weeks postresult. Participants who decline testing are sent a questionnaire regarding reasons for declining. Participants with a B-JFM are sent questionnaires 12-month and 24-month post-testing. The questionnaires incorporate validated scales, which measure anxiety, decisional conflict and regret, and test-related distress and positive experiences, and other items specifically developed or adapted for the study. These measures will be assessed for each programme and the two population-based B-JFM screening methods will be compared.Ethics and disseminationInstitutional Human Research Ethics Committee approval was obtained from the South Eastern Area Health Service Human Research Ethics Committee: HREC Ref 16/125.Following the analysis of the study results, the findings will be disseminated widely through conferences and publications, and directly to participants in writing.

Megan Best, Phyllis Butow, Chris Jacobs, Ilona Juraskova, Jacqueline Savard, Bettina Meiser, David Goldstein, Mandy Ballinger, Nicci Bartley, Christine Napier, Grace Davies, David Thomas, Kathy Tucker, Timothy Schlub, Ainsley J. Newson, (2020)Advanced cancer patient preferences for receiving molecular profiling results, In: Psycho-oncology (Chichester, England)29(10)pp. 1533-1539 Wiley

Objective This study aimed to discern preferences for receiving somatic molecular profiling (MP) results in cancer patients who have given consent to undergo testing. Methods We conducted a mixed-methods study to explore patients' views on which MP results they would like to receive and why. Advanced cancer patients (n = 1299) completed questionnaires after giving consent to participate in a parent genomics study and undergoing MP. A subset of patients (n = 20) participated in qualitative interviews. Results Almost all (96%) participants were interested in receiving results which would direct cancer treatment (ie, were actionable). A smaller majority wanted to access results which were not actionable (64%) or were variants of unknown significance (60%). Most (86%) were interested in finding out about germline findings, though not as a priority. Themes identified in interview data were: (a) Cancer is the focus; (b) Trust in clinicians; and (c) Respect for a right not to know. Conclusions The majority of advanced cancer patients undergoing MP prioritised results which would lead to treatment options. They trusted their oncologists to help them navigate the results return process. While there was interest in knowing about other results, this was a lesser priority. Nevertheless, given high levels of interest in receiving all results, ethical aspects of not providing uninformative results requires further research, including a consideration of patient rationales for desiring this information and what health professionals can and should do to support patients in the absence of meaningful information being available.

C Jacobs, R Rawson, C Campion, C Caulfield, J Heath, C Burton, F Kavalier (2007)Providing a community-based cancer risk assessment service for a socially and ethnically diverse population, In: Familial cancer6(2)pp. 189-195

BACKGROUNDPatients from ethnic minorities are under-represented in referrals to cancer genetics services. In a regional genetics centre that serves two London boroughs, the existing service attracts 3% of its referrals from Black and Minority Ethnic (BME) and other ethnic groups, despite the fact that these groups make up 34% of the population.OBJECTIVESTo improve access to familial cancer risk assessment in a socially and ethnically diverse population.SETTINGThe London boroughs of Lambeth and Southwark.DESIGNCommunity-based, nurse-led clinics were established for people who were concerned about their familial cancer risk. Patients were asked to triage themselves by answering three questions. Self-referral was encouraged.MAIN OUTCOME MEASURESData were gathered on ethnicity of clients, cancer risk, source of referral and patient and health professional satisfaction with the service.RESULTSOf the 415 people who have accessed the service, 46% were from not White British groups and 67% referred themselves to the service, demonstrating the success of this model in reaching 'hard to reach' groups. Thirty-seven percent of patients were assessed as being at population risk and 63% were assessed as being at moderate risk or higher, showing that the clinics were meeting an unmet need in the community.

Stephanie White, Erin Turbitt, Kris Rogers, Kathy Tucker, Alison McEwen, Megan Best, Jane L. L. Phillips, Chris Jacobs (2023)A survey of genetic and palliative care health professionals' views of integrating genetics into palliative care, In: European journal of human genetics : EJHG Springer Nature

Genetic counselling and testing have utility for people with palliative care needs and their families. However, genetic and palliative care health professionals have described difficulties initiating palliative-genetic discussions. Between March and July 2022, we received n = 73 surveys (6% response rate) from genetic and palliative care health professionals in Australia and New Zealand that assessed and compared barriers and facilitators. The main perceived barrier to both groups was palliative care health professionals' lack of genetic knowledge (44%). Most palliative care health professionals were 'not at all confident' performing several activities, including discussing DNA banking (52%) and knowing their legal responsibilities when sharing genetic information (58%). The most frequently selected facilitator for genetic health professionals was fostering close relationships with palliative care health professionals (52%), while palliative care health professionals indicated a genetic referral template (51%) would be of assistance. Almost all participants agreed genetic discussions do not undermine the central ethos of palliative care (87%). Fewer palliative care health professionals considered themselves well situated to have genetic discussions with a palliative patient's family compared to genetic health professionals (p = 0.014). Our results suggest that genetic and palliative care health professionals support integrating genetics into palliative care, although refinement of the palliative care health professionals' role in this process is required. We have identified intervention targets to overcome barriers related to knowledge and confidence, which ought to be integrated into future interventions designed to support health professionals deliver the benefits of genetic information to people with palliative care needs and their families.

Susan J. Ramus, Chris Jacobs, Antonis C Antoniou, Karoline B. Kuchenbaecker, Penny Soucy, Jonathan Beesley, Xiaoqing Chen, Lesley McGuffog, Olga M. Sinilnikova, Sue Healey, Daniel Barrowdale, Andrew Lee, Mads Thomassen, Anne-Marie Gerdes, Torben A. Kruse, Uffe Birk Jensen, Anne-Bine Skytte, Maria A. Caligo, Annelie Liljegren, Annika Lindblom, Håkan Olsson, Ulf Kristoffersson, Marie Stenmark-Askmalm, Beatrice Melin, Susan M. Domchek, Katherine L. Nathanson, Timothy R. Rebbeck, Anna Jakubowska, Jan Lubinski, Katarzyna Jaworska, Katarzyna Durda, Elżbieta Złowocka, Jacek Gronwald, Tomasz Huzarski, Tomasz Byrski, Cezary Cybulski, Aleksandra Toloczko-Grabarek, Ana Osorio, Javier Benitez, Mercedes Duran, Maria-Isabel Tejada, Ute Hamann, Matti Rookus, Flora E. van Leeuwen, Cora M. Aalfs, Hanne E.J. Meijers-Heijboer, Christi J. van Asperen, K.E.P. van Roozendaal, Nicoline Hoogerbrugge, J. Margriet Collée, Mieke Kriege, Rob B. van der Luijt, Susan Peock, Debra Frost, Steve D. Ellis, Radka Platte, Elena Fineberg, D. Gareth Evans, Fiona Lalloo, Ros Eeles, Julian Adlard, Rosemarie Davidson, Diana Eccles, Trevor Cole, Jackie Cook, Joan Paterson, Fiona Douglas, Carole Brewer, Shirley Hodgson, Patrick J. Morrison, Lisa Walker, Mary E. Porteous, M. John Kennedy, Harsh Pathak, Andrew K. Godwin, Dominique Stoppa-Lyonnet, Virginie Caux-Moncoutier, Antoine de Pauw, Marion Gauthier-Villars, Sylvie Mazoyer, Mélanie Léoné, Alain Calender, Christine Lasset, Valérie Bonadona, Agnès Hardouin, Pascaline Berthet, Yves-Jean Bignon, Nancy Uhrhammer, Laurence Faivre, Catherine Loustalot, Saundra Buys, Mary Daly, Alex Miron, Mary Beth Terry, Wendy K. Chung, Esther M John, Melissa Southey, David Goldgar, Christian F Singer, Muy-Kheng Tea, Georg Pfeiler, Anneliese Fink-Retter, Thomas v. O. Hansen, Bent Ejlertsen, Oskar Th Johannsson, Kenneth Offit, Tomas Kirchhoff, Mia M. Gaudet, Joseph Vijai, Mark Robson, Marion Piedmonte, Kelly-Anne Phillips, Linda Van Le, James S Hoffman, Amanda Ewart Toland, Marco Montagna, Silvia Tognazzo, Evgeny Imyanitov, Claudine Isaacs, Ramunas Janavicius, Conxi Lazaro, Ignacio Blanco, Eva Tornero, Matilde Navarro, Kirsten B. Moysich, Beth Y. Karlan, Jenny Gross, Edith Olah, Tibor Vaszko, Soo-Hwang Teo, Patricia A. Ganz, Mary S. Beattie, Cecelia M Dorfling, Elizabeth J van Rensburg, Orland Diez, Ava Kwong, Rita K. Schmutzler, Barbara Wappenschmidt, Christoph Engel, Alfons Meindl, Nina Ditsch, Norbert Arnold, Simone Heidemann, Dieter Niederacher, Sabine Preisler-Adams, Dorotehea Gadzicki, Raymonda Varon-Mateeva, Helmut Deissler, Andrea Gehrig, Christian Sutter, Karin Kast, Britta Fiebig, Dieter Schäfer, Trinidad Caldes, Miguel de la Hoya, Heli Nevanlinna, Kristiina Aittomäki, Marie Plante, Amanda B. Spurdle, Susan L. Neuhausen, Yuan Chun Ding, Xianshu Wang, Noralane Lindor, Zachary Fredericksen, V. Shane Pankratz, Paolo Peterlongo, Siranoush Manoukian, Bernard Peissel, Daniela Zaffaroni, Bernardo Bonanni, Loris Bernard, Riccardo Dolcetti, Laura Papi, Laura Ottini, Paolo Radice, Mark H. Greene, Phuong L. Mai, Irene L. Andrulis, Gord Glendon, Hilmi Ozcelik, Paul D.P. Pharoah, Simon A. Gayther, Jacques Simard, Douglas F. Easton, Fergus J. Couch, Georgia Chenevix-Trench (2012)Ovarian Cancer Susceptibility Alleles and Risk of Ovarian Cancer in BRCA1 and BRCA2 Mutation Carriers, In: Human mutation33(4)pp. 690-702

Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Four single-nucleotide polymorphisms (SNPs), rs10088218 (at 8q24), rs2665390 (at 3q25), rs717852 (at 2q31), and rs9303542 (at 17q21), were genotyped in 12,599 BRCA1 and 7,132 BRCA2 carriers, including 2,678 ovarian cancer cases. Associations were evaluated within a retrospective cohort approach. All four loci were associated with ovarian cancer risk in BRCA2 carriers; rs10088218 per-allele hazard ratio (HR) = 0.81 (95% CI: 0.67–0.98) P-trend = 0.033, rs2665390 HR = 1.48 (95% CI: 1.21–1.83) P-trend = 1.8 × 10 −4 , rs717852 HR = 1.25 (95% CI: 1.10–1.42) P-trend = 6.6 × 10 −4 , rs9303542 HR = 1.16 (95% CI: 1.02–1.33) P-trend = 0.026. Two loci were associated with ovarian cancer risk in BRCA1 carriers; rs10088218 per-allele HR = 0.89 (95% CI: 0.81–0.99) P-trend = 0.029, rs2665390 HR = 1.25 (95% CI: 1.10–1.42) P-trend = 6.1 × 10 −4 . The HR estimates for the remaining loci were consistent with odds ratio estimates for the general population. The identification of multiple loci modifying ovarian cancer risk may be useful for counseling women with BRCA1 and BRCA2 mutations regarding their risk of ovarian cancer.

Sophie Blein, Christine June Jacobs, Claire Bardel, Vincent Danjean, Lesley McGuffog, Sue Healey, Daniel Barrowdale, Andrew Lee, Joe Dennis, Karoline B Kuchenbaecker, Penny Soucy, Mary Beth Terry, Wendy K Chung, David E Goldgar, Saundra S Buys, Ramunas Janavicius, Laima Tihomirova, Nadine Tung, Cecilia M Dorfling, Elizabeth J van Rensburg, Susan L Neuhausen, Yuan Chun Ding, Anne-Marie Gerdes, Bent Ejlertsen, Finn C Nielsen, Thomas Vo Hansen, Ana Osorio, Javier Benitez, Raquel Andrés Conejero, Ena Segota, Jeffrey N Weitzel, Margo Thelander, Paolo Peterlongo, Paolo Radice, Valeria Pensotti, Riccardo Dolcetti, Bernardo Bonanni, Bernard Peissel, Daniela Zaffaroni, Giulietta Scuvera, Siranoush Manoukian, Liliana Varesco, Gabriele L Capone, Laura Papi, Laura Ottini, Drakoulis Yannoukakos, Irene Konstantopoulou, Judy Garber, Ute Hamann, Alan Donaldson, Angela Brady, Carole Brewer, Claire Foo, D Gareth Evans, Debra Frost, Diana Eccles, Fiona Douglas, Jackie Cook, Julian Adlard, Julian Barwell, Lisa Walker, Louise Izatt, Lucy E Side, M John Kennedy, Marc Tischkowitz, Mark T Rogers, Mary E Porteous, Patrick J Morrison, Radka Platte, Ros Eeles, Rosemarie Davidson, Shirley Hodgson, Trevor Cole, Andrew K Godwin, Claudine Isaacs, Kathleen Claes, Kim De Leeneer, Alfons Meindl, Andrea Gehrig, Barbara Wappenschmidt, Christian Sutter, Christoph Engel, Dieter Niederacher, Doris Steinemann, Hansjoerg Plendl, Karin Kast, Kerstin Rhiem, Nina Ditsch, Norbert Arnold, Raymonda Varon-Mateeva, Rita K Schmutzler, Sabine Preisler-Adams, Nadja Bogdanova Markov, Shan Wang-Gohrke, Antoine de Pauw, Cédrick Lefol, Christine Lasset, Dominique Leroux, Etienne Rouleau, Francesca Damiola, Hélène Dreyfus, Laure Barjhoux, Lisa Golmard, Nancy Uhrhammer, Valérie Bonadona, Valérie Sornin, Yves-Jean Bignon, Jonathan Carter, Linda Van Le, Marion Piedmonte, Paul A DiSilvestro, Miguel de la Hoya, Trinidad Caldes, Heli Nevanlinna, Kristiina Aittomäki, Agnes Jager, Ans Mw van den Ouweland, Carolien M Kets, Cora M Aalfs, Flora E van Leeuwen, Frans Bl Hogervorst, Hanne Ej Meijers-Heijboer, Jan C Oosterwijk, Kees Ep van Roozendaal, Matti A Rookus, Peter Devilee, Rob B van der Luijt, Edith Olah, Orland Diez, Alex Teulé, Conxi Lazaro, Ignacio Blanco, Jesús Del Valle, Anna Jakubowska, Grzegorz Sukiennicki, Jacek Gronwald, Jan Lubinski, Katarzyna Durda, Katarzyna Jaworska-Bieniek, Bjarni A Agnarsson, Christine Maugard, Alberto Amadori, Marco Montagna, Manuel R Teixeira, Amanda B Spurdle, William Foulkes, Curtis Olswold, Noralane M Lindor, Vernon S Pankratz, Csilla I Szabo, Anne Lincoln, Lauren Jacobs, Marina Corines, Mark Robson, Joseph Vijai, Andreas Berger, Anneliese Fink-Retter, Christian F Singer, Christine Rappaport, Daphne Geschwantler Kaulich, Georg Pfeiler, Muy-Kheng Tea, Mark H Greene, Phuong L Mai, Gad Rennert, Evgeny N Imyanitov, Anna Marie Mulligan, Gord Glendon, Irene L Andrulis, Sandrine Tchatchou, Amanda Ewart Toland, Inge Sokilde Pedersen, Mads Thomassen, Torben A Kruse, Uffe Birk Jensen, Maria A Caligo, Eitan Friedman, Jamal Zidan, Yael Laitman, Annika Lindblom, Beatrice Melin, Brita Arver, Niklas Loman, Richard Rosenquist, Olufunmilayo I Olopade, Robert L Nussbaum, Susan J Ramus, Katherine L Nathanson, Susan M Domchek, Timothy R Rebbeck, Banu K Arun, Gillian Mitchell, Beth Y Karlan, Jenny Lester, Sandra Orsulic, Dominique Stoppa-Lyonnet, Gilles Thomas, Jacques Simard, Fergus J Couch, Kenneth Offit, Douglas F Easton, Georgia Chenevix-Trench, Antonis C Antoniou, Sylvie Mazoyer, Catherine M Phelan, Olga M Sinilnikova, David G Cox (2015)An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers, In: Breast cancer research : BCR17(1)61pp. 61-61

Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.

Travel restrictions, physical distancing, and limits to clinical placements due to the global pandemic raised enormous challenges for genetic counseling education in 2020. In response, we created authentic virtual clinical experiences in our Master of Genetic Counseling program, mimicking clinical practice: virtual simulation with standardized clients, and virtual clinical placements, including intake calls, triage, consultations, teamwork and time management, and genetic counseling with standardized clients. The virtual clinical experiences involved online pre-brief, simulation, and debrief. We aimed to evaluate students' satisfaction with this learning method. Between April and November 2020, we distributed an anonymous online survey to all participating students using a modified version of a validated satisfaction with simulation scale. We analyzed the combined responses from first-and second-year virtual clinical experiences using descriptive statistics and content analysis. The total number of possible responses was 120. The mean response rate was 68.36% (n = 82.03), with a mean of 16.41 participants responding to each survey from each year group. Of the first-year participants, 53% (n = 10) had not observed a genetic counseling consultation before attending the virtual clinical placement. Overall, 92.5% of responses indicated that students were satisfied with the virtual clinical experiences (SD = 0.05). 100% (n = 82) of responses indicated that working with standardized clients was beneficial to learning, encouraged reflection on clinical ability and was a valuable learning experience overall. However, 37.78% (n = 17) of those who participated in the virtual simulation found that the use of Zoom detracted from their clinical learning. The virtual clinical experiences increased first-year students' confidence about clinical placement and prepared second-year students for telehealth. In conclusion, the adaptation to virtual clinical experiences enhanced learning for most students, prepared them for practice, met the requirements of the accreditation body and enabled all of our final year students to graduate on time.

Chris Jacobs, Caroline Dancyger, Jonathan A. Smith, Susan Michie (2015)Accuracy of recall of information about a cancer-predisposing BRCA1/2 gene mutation among patients and relatives, In: European journal of human genetics : EJHG23(2)147pp. 147-151 Springer Nature

This observational study aimed to (i) compare the accuracy of information recalled by patients and relatives following genetic counselling about a newly identified BRCA1/2 mutation, (ii) identify differences in accuracy of information about genetics and hereditary cancer and (iii) investigate whether accuracy among relatives improved when information was provided directly by genetics health professionals. Semistructured interviews following results from consultations with 10 breast/ovarian cancer patients and 22 relatives were audio-recorded and transcribed. Information provided by the genetics health professional was tracked through the families and coded for accuracy. Accuracy was analysed using the Wilcoxon Signed-Ranks test. Sources of information were tested using Spearman's rank-order correlation coefficient. Fifty-three percent of the information recalled by patients was accurate. Accuracy of recall among relatives was significantly lower than that among patients (P = 0.017). Both groups recalled a lower proportion of information about hereditary cancer than about genetics (P = 0.005). Relatives who learnt the information from the patient alone recalled significantly less accurate information than those informed directly by genetics health professionals (P = 0.001). Following genetic counselling about a BRCA1/2 mutation, accuracy of recall was low among patients and relatives, particularly about hereditary cancer. Multiple sources of information, including direct contact with genetics health professionals, may improve the accuracy of information among relatives.

Ebony Richardson, Alison McEwen, Toby Newton-John, Ashley Crook, Chris Jacobs (2022)Incorporating patient perspectives in the development of a core outcome set for reproductive genetic carrier screening: a sequential systematic review, In: European journal of human genetics : EJHG30(7)pp. 756-765

There is currently no consensus on the key outcomes of reproductive genetic carrier screening (RGCS). This has led to a large amount of variability in approaches to research, limiting direct comparison and synthesis of findings. In a recently published systematic review of quantitative studies on RGCS, we found that few studies incorporated patient-reported outcomes. In response to this gap, we conducted a sequential systematic review of qualitative studies to identify outcomes exploring the patient experience of RGCS. In conjunction with the review of quantitative studies, these outcomes will be used to inform the development of a core outcome set. Text excerpts relevant to outcomes, including quotes and themes, were extracted verbatim and deductively coded as outcomes. We conducted a narrative synthesis to group outcomes within domains previously defined in our review of quantitative studies, and identify any new domains that were unique to qualitative studies. Seventy-eight outcomes were derived from qualitative studies and grouped into 19 outcome domains. Three new outcome domains were identified; 'goals of pre- and post-test genetic counselling', 'acceptability of further testing and alternative reproductive options', and 'perceived utility of RGCS'. The identification of outcome domains that were not identified in quantitative studies indicates that outcomes reflecting the patient perspective may be under-represented in the quantitative literature on this topic. Further work should focus on ensuring that outcomes reflect the real world needs and concerns of patients in order to maximise translation of research findings into clinical practice.

Jonathan A. Smith, Caroline Dancyger, Melissa Wallace, Chris Jacobs, Susan Michie (2011)The Development of a Methodology for Examining the Process of Family Communication of Genetic Test Results, In: Journal of genetic counseling20(1)23pp. 23-34 Wiley

It is important to study communication processes in families where members are undergoing testing for genetic conditions because the information received from such testing is crucial not just to the individual concerned but also to other members of the biological family. This topic has received little research attention, in part because of the complexities of methodology required. In this paper we present the development of a method specifically designed for the examination of the content and process of communication of genetic information in families. The method aims to maximize ecological validity as far as is possible. We describe how participants and other family members are recruited and how data were collected. We outline three main data analytic strategies: a graphic to show how genetic information changes as it flows from clinic and through the family, an intensive qualitative analysis of the meaning and impact of the genetic information to different family members, and an informative genogram which plots key family dynamics. This method will be illustrated in relation to a study of ten family-groups where one individual has been found to carry a genetic mutation predisposing them to hereditary breast and ovarian cancer.

Ranjit Manchanda, Rosa Legood, Matthew Burnell, Alistair McGuire, Maria Raikou, Kelly Loggenberg, Jane Wardle, Saskia Sanderson, Sue Gessler, Lucy Side, Nyala Balogun, Rakshit Desai, Ajith Kumar, Huw Dorkins, Yvonne Wallis, Cyril Chapman, Rohan Taylor, Chris Jacobs, Ian Tomlinson, Uziel Beller, Usha Menon, Ian Jacobs (2015)Cost-effectiveness of population screening for BRCA mutations in Ashkenazi jewish women compared with family history-based testing, In: JNCI : Journal of the National Cancer Institute107(1)380pp. 380-380

Population-based testing for BRCA1/2 mutations detects the high proportion of carriers not identified by cancer family history (FH)-based testing. We compared the cost-effectiveness of population-based BRCA testing with the standard FH-based approach in Ashkenazi Jewish (AJ) women. A decision-analytic model was developed to compare lifetime costs and effects amongst AJ women in the UK of BRCA founder-mutation testing amongst: 1) all women in the population age 30 years or older and 2) just those with a strong FH (≥10% mutation risk). The model assumes that BRCA carriers are offered risk-reducing salpingo-oophorectomy and annual MRI/mammography screening or risk-reducing mastectomy. Model probabilities utilize the Genetic Cancer Prediction through Population Screening trial/published literature to estimate total costs, effects in terms of quality-adjusted life-years (QALYs), cancer incidence, incremental cost-effectiveness ratio (ICER), and population impact. Costs are reported at 2010 prices. Costs/outcomes were discounted at 3.5%. We used deterministic/probabilistic sensitivity analysis (PSA) to evaluate model uncertainty. Compared with FH-based testing, population-screening saved 0.090 more life-years and 0.101 more QALYs resulting in 33 days' gain in life expectancy. Population screening was found to be cost saving with a baseline-discounted ICER of -£2079/QALY. Population-based screening lowered ovarian and breast cancer incidence by 0.34% and 0.62%. Assuming 71% testing uptake, this leads to 276 fewer ovarian and 508 fewer breast cancer cases. Overall, reduction in treatment costs led to a discounted cost savings of £3.7 million. Deterministic sensitivity analysis and 94% of simulations on PSA (threshold £20000) indicated that population screening is cost-effective, compared with current NHS policy. Population-based screening for BRCA mutations is highly cost-effective compared with an FH-based approach in AJ women age 30 years and older.

Nicci Bartley, Megan Best, Chris Jacobs, Ilona Juraskova, Ainsley J Newson, Jacqueline Savard, Bettina Meiser, Mandy L Ballinger, David M Thomas, Barbara Biesecker, Phyllis Butow (2020)Cancer patients’ views and understanding of genome sequencing: a qualitative study, In: Journal of medical genetics57(10)pp. 671-676

BackgroundLittle is known about knowledge of, and attitudes towards, genome sequencing (GS) among individuals with a personal history of cancer who decide to undergo GS. This qualitative study aimed to investigate baseline knowledge and attitudes among individuals previously diagnosed with a cancer of likely genetic origin who have consented to GS.MethodsSemistructured interviews were conducted with purposively selected participants (n=20) from the longitudinal Psychosocial Issues in Genomic Oncology study, within a month of consenting to GS and prior to receiving any results. Participants were adults with a cancer of likely genetic aetiology who are undertaking GS as part of a larger genetic study.ResultsAnalysis identified three main themes: limited understanding of genomics; multifactorial motivation; and complex decision making. While motivations such as obtaining health information about self and family appear to be the main drivers for undertaking GS, these motivations are sometimes based on limited knowledge of the accuracy and utility of GS, creating unrealistic expectations. This in turn can prolong the deliberation process and lead to ongoing decisional conflict.ConclusionUnderstanding the degree and nature of patient understanding of GS, as well as their attitudes and decision-making processes, will enable healthcare professionals to better manage patient expectations and appropriately engage and support patients to make an informed decision when pursuing GS.

Louise Izatt, Jill Greenman, Shirley Hodgson, David Ellis, Sally Watts, Gillian Scott, Chris Jacobs, Rachael Liebmann, Marketa J. Zvelebil, Christopher Mathew, Ellen Solomon (1999)Identification of germline missense mutations and rare allelic variants in the ATM gene in early-onset breast cancer, In: Genes chromosomes & cancer26(4)pp. 286-294 John Wiley & Sons, Inc
Chris Jacobs, Christine Patch, Susan Michie (2019)Communication about genetic testing with breast and ovarian cancer patients: a scoping review, In: European journal of human genetics : EJHG27(4)pp. 511-524 Springer Nature

Genetic testing of patients with cancer is increasingly offered to guide management, resulting in a growing need for oncology health professionals to communicate genetics information and facilitate informed decision-making in a short time frame. This scoping review aimed to map and synthesise what is known about health professionals' communication about genetic testing for hereditary breast and ovarian cancer with cancer patients. Four databases were systematically searched using a recognised scoping review method. Areas and types of research were mapped and a narrative synthesis of the findings was undertaken. Twenty-nine papers from 25 studies were included. Studies were identified about (i) information needs, (ii) process and content of genetic counselling, (iii) cognitive and emotional impact, including risk perception and recall, understanding and interpretation of genetic test results, and anxiety and distress, (iv) patients' experiences, (v) communication shortly after diagnosis and (vi) alternatives to face-to-face genetic counselling. Patients' need for cancer-focused, personalised information is not always met by genetic counselling. Genetic counselling tends to focus on biomedical information at the expense of psychological support. For most patients, knowledge is increased and anxiety is not raised by pre-test communication. However, some patients experience anxiety and distress when results are disclosed, particularly those tested shortly after diagnosis who are unprepared or unsupported. For many patients, pre-test communication by methods other than face-to-face genetic counselling is acceptable. Research is needed to identify patients who may benefit from genetic counselling and support and to investigate communication about hereditary breast and ovarian cancer by oncology health professionals.

Megan Best, Ainsley J. Newson, Bettina Meiser, Ilona Juraskova, David Goldstein, Kathy Tucker, Mandy L. Ballinger, Dominique Hess, Timothy E. Schlub, Barbara Biesecker, Richard Vines, Kate Vines, David Thomas, Mary-Anne Young, Jacqueline Savard, Chris Jacobs, Phyllis Butow (2018)The PiGeOn project: protocol of a longitudinal study examining psychosocial and ethical issues and outcomes in germline genomic sequencing for cancer, In: BMC cancer18(1)454pp. 454-454 Springer Nature

Background: Advances in genomics offer promise for earlier detection or prevention of cancer, by personalisation of medical care tailored to an individual's genomic risk status. However genome sequencing can generate an unprecedented volume of results for the patient to process with potential implications for their families and reproductive choices. This paper describes a protocol for a study (PiGeOn) that aims to explore how patients and their blood relatives experience germline genomic sequencing, to help guide the appropriate future implementation of genome sequencing into routine clinical practice. Methods: We have designed a mixed-methods, prospective, cohort sub-study of a germline genomic sequencing study that targets adults with cancer suggestive of a genetic aetiology. One thousand probands and 2000 of their blood relatives will undergo germline genomic sequencing as part of the parent study in Sydney, Australia between 2016 and 2020. Test results are expected within 12-15 months of recruitment. For the PiGeOn sub-study, participants will be invited to complete surveys at baseline, three months and twelve months after baseline using self-administered questionnaires, to assess the experience of long waits for results (despite being informed that results may not be returned) and expectations of receiving them. Subsets of both probands and blood relatives will be purposively sampled and invited to participate in three semi-structured qualitative interviews (at baseline and each follow-up) to triangulate the data. Ethical themes identified in the data will be used to inform critical revisions of normative ethical concepts or frameworks. Discussion: This will be one of the first studies internationally to follow the psychosocial impact on probands and their blood relatives who undergo germline genome sequencing, over time. Study results will inform ongoing ethical debates on issues such as informed consent for genomic sequencing, and informing participants and their relatives of specific results. The study will also provide important outcome data concerning the psychological impact of prolonged waiting for germline genomic sequencing. These data are needed to ensure that when germline genomic sequencing is introduced into standard clinical settings, ethical concepts are embedded, and patients and their relatives are adequately prepared and supported during and after the testing process.

Ranjit Manchanda, Matthew Burnell, Kelly Loggenberg, Rakshit Desai, Jane Wardle, Saskia C Sanderson, Sue Gessler, Lucy Side, Nyala Balogun, Ajith Kumar, Huw Dorkins, Yvonne Wallis, Cyril Chapman, Ian Tomlinson, Rohan Taylor, Chris Jacobs, Rosa Legood, Maria Raikou, Alistair McGuire, Uziel Beller, Usha Menon, Ian Jacobs (2016)Cluster-randomised non-inferiority trial comparing DVD-assisted and traditional genetic counselling in systematic population testing for BRCA1/2 mutations, In: Journal of medical genetics53(7)472pp. 472-480

BackgroundNewer approaches to genetic counselling are required for population-based testing. We compare traditional face-to-face genetic counselling with a DVD-assisted approach for population-based BRCA1/2 testing.MethodsA cluster-randomised non-inferiority trial in the London Ashkenazi Jewish population.Inclusion criteriaAshkenazi Jewish men/women >18 years; exclusion criteria: (a) known BRCA1/2 mutation, (b) previous BRCA1/2 testing and (c) first-degree relative of BRCA1/2 carrier. Ashkenazi Jewish men/women underwent pre-test genetic counselling prior to BRCA1/2 testing in the Genetic Cancer Prediction through Population Screening trial (ISRCTN73338115). Genetic counselling clinics (clusters) were randomised to traditional counselling (TC) and DVD-based counselling (DVD-C) approaches. DVD-C involved a DVD presentation followed by shorter face-to-face genetic counselling. Outcome measures included genetic testing uptake, cancer risk perception, increase in knowledge, counselling time and satisfaction (Genetic Counselling Satisfaction Scale). Random-effects models adjusted for covariates compared outcomes between TC and DVD-C groups. One-sided 97.5% CI was used to determine non-inferiority. Secondary outcomes: relevance, satisfaction, adequacy, emotional impact and improved understanding with the DVD; cost-minimisation analysis for TC and DVD-C approaches.Results936 individuals (clusters=256, mean-size=3.6) were randomised to TC (n=527, clusters=134) and DVD-C (n=409, clusters=122) approaches. Groups were similar at baseline, mean age=53.9 (SD=15) years, women=66.8%, men=33.2%. DVD-C was non-inferior to TC for increase in knowledge (d=−0.07; lower 97.5% CI=−0.41), counselling satisfaction (d=−0.38, 97.5% CI=1.2) and risk perception (d=0.08; upper 97.5% CI=3.1). Group differences and CIs did not cross non-inferiority margins. DVD-C was equivalent to TC for uptake of genetic testing (d=−3%; lower/upper 97.5% CI −7.9%/1.7%) and superior for counselling time (20.4 (CI 18.7 to 22.2) min reduction (p

R Manchanda, M Burnell, F Gaba, S Sanderson, K Loggenberg, S Gessler, J Wardle, L Side, R Desai, A F Brady, H Dorkins, Y Wallis, C Chapman, C Jacobs, I Tomlinson, U Beller, U Menon, I Jacobs (2019)Attitude towards and factors affecting uptake of population-based BRCA testing in the Ashkenazi Jewish population: a cohort study, In: BJOG : an international journal of obstetrics and gynaecology126(6)pp. 784-794

To evaluate factors affecting unselected population-based BRCA testing in Ashkenazi Jews (AJ). Cohort-study set within recruitment to the GCaPPS trial (ISRCTN73338115). North London AJ population. Ashkenazi Jews women/men >18 years, recruited through self-referral. Ashkenazi Jews women/men underwent pre-test counselling for BRCA testing through recruitment clinics (clusters). Consenting individuals provided blood samples for BRCA testing. Data were collected on socio-demographic/family history/knowledge/psychological well-being along with benefits/risks/cultural influences (18-item questionnaire measuring 'attitude'). Four-item Likert-scales analysed initial 'interest' and 'intention-to-test' pre-counselling. Uni- and multivariable logistic regression models evaluated factors affecting uptake/interest/intention to undergo BRCA testing. Statistical inference was based on cluster robust standard errors and joint Wald tests for significance. Item-Response Theory and graded-response models modelled responses to 18-item questionnaire. Interest, intention, uptake, attitude towards BRCA testing. A total of 935 individuals (women = 67%/men = 33%; mean age = 53.8 (SD = 15.02) years) underwent pre-test genetic-counselling. During the pre-counselling, 96% expressed interest in and 60% indicated a clear intention to undergo BRCA testing. Subsequently, 88% opted for BRCA testing. BRCA-related knowledge (P = 0.013) and degree-level education (P = 0.01) were positively and negatively (respectively) associated with intention-to-test. Being married/cohabiting had four-fold higher odds for BRCA testing uptake (P = 0.009). Perceived benefits were associated with higher pre-counselling odds for interest in and intention to undergo BRCA testing. Reduced uncertainty/reassurance were the most important factors contributing to decision-making. Increased importance/concern towards risks/limitations (confidentiality/insurance/emotional impact/inability to prevent cancer/marriage ability/ethnic focus/stigmatisation) were significantly associated with lower odds of uptake of BRCA testing, and discriminated between acceptors and decliners. Male gender/degree-level education (P = 0.001) had weaker correlations, whereas having children showed stronger (P = 0.005) associations with attitudes towards BRCA testing. BRCA testing in the AJ population has high acceptability. Pre-test counselling increases awareness of disadvantages/limitations of BRCA testing, influencing final cost-benefit perception and decision-making on undergoing testing. BRCA testing in Ashkenazi Jews has high acceptability and uptake. Pre-test counselling facilitates informed decision-making.

Ignacio Blanco, Chris Jacobs, Karoline Kuchenbaecker, Daniel Cuadras, Xianshu Wang, Daniel Barrowdale, Gorka Ruiz de Garibay, Pablo Librado, Alejandro Sánchez-Gracia, Julio Rozas, Núria Bonifaci, Lesley McGuffog, Vernon S Pankratz, Abul Islam, Francesca Mateo, Antoni Berenguer, Anna Petit, Isabel Català, Joan Brunet, Lidia Feliubadaló, Eva Tornero, Javier Benítez, Ana Osorio, Teresa Ramón y Cajal, Heli Nevanlinna, Kristiina Aittomäki, Banu K Arun, Amanda E Toland, Beth Y Karlan, Christine Walsh, Jenny Lester, Mark H Greene, Phuong L Mai, Robert L Nussbaum, Irene L Andrulis, Susan M Domchek, Katherine L Nathanson, Timothy R Rebbeck, Rosa B Barkardottir, Anna Jakubowska, Jan Lubinski, Katarzyna Durda, Katarzyna Jaworska-Bieniek, Kathleen Claes, Tom Van Maerken, Orland Díez, Thomas V Hansen, Lars Jønson, Anne-Marie Gerdes, Bent Ejlertsen, Miguel de la Hoya, Trinidad Caldés, Alison M Dunning, Clare Oliver, Elena Fineberg, Margaret Cook, Susan Peock, Emma McCann, Alex Murray, Gabriella Pichert, Fiona Lalloo, Carol Chu, Huw Dorkins, Joan Paterson, Kai-Ren Ong, Manuel R Teixeira, Frans B L Hogervorst, Annemarie H van der Hout, Caroline Seynaeve, Rob B van der Luijt, Marjolijn J L Ligtenberg, Peter Devilee, Juul T Wijnen, Matti A Rookus, Hanne E J Meijers-Heijboer, Marinus J Blok, Ans M W van den Ouweland, Cora M Aalfs, Gustavo C Rodriguez, Kelly-Anne A Phillips, Marion Piedmonte, Stacy R Nerenstone, Victoria L Bae-Jump, David M O'Malley, Elena S Ratner, Rita K Schmutzler, Barbara Wappenschmidt, Kerstin Rhiem, Christoph Engel, Alfons Meindl, Nina Ditsch, Norbert Arnold, Hansjoerg J Plendl, Dieter Niederacher, Christian Sutter, Shan Wang-Gohrke, Doris Steinemann, Sabine Preisler-Adams, Karin Kast, Raymonda Varon-Mateeva, Andrea Gehrig, Anders Bojesen, Inge Sokilde Pedersen, Lone Sunde, Uffe Birk Jensen, Mads Thomassen, Torben A Kruse, Lenka Foretova, Paolo Peterlongo, Loris Bernard, Bernard Peissel, Giulietta Scuvera, Siranoush Manoukian, Paolo Radice, Laura Ottini, Marco Montagna, Simona Agata, Christine Maugard, Jacques Simard, Penny Soucy, Andreas Berger, Anneliese Fink-Retter, Christian F Singer, Christine Rappaport, Daphne Geschwantler-Kaulich, Muy-Kheng Tea, Georg Pfeiler, Esther M John, Alex Miron, Susan L Neuhausen, Mary Beth Terry, Wendy K Chung, Mary B Daly, David E Goldgar, Ramunas Janavicius, Cecilia M Dorfling, Elisabeth J van Rensburg, Florentia Fostira, Irene Konstantopoulou, Judy Garber, Andrew K Godwin, Edith Olah, Steven A Narod, Gad Rennert, Shani Shimon Paluch, Yael Laitman, Eitan Friedman, Annelie Liljegren, Johanna Rantala, Marie Stenmark-Askmalm, Niklas Loman, Evgeny N Imyanitov, Ute Hamann, Amanda B Spurdle, Sue Healey, Jeffrey N Weitzel, Josef Herzog, David Margileth, Chiara Gorrini, Manel Esteller, Antonio Gómez, Sergi Sayols, Enrique Vidal, Holger Heyn, Dominique Stoppa-Lyonnet, Melanie Léoné, Laure Barjhoux, Marion Fassy-Colcombet, Antoine de Pauw, Christine Lasset, Sandra Fert Ferrer, Laurent Castera, Pascaline Berthet, François Cornelis, Yves-Jean Bignon, Francesca Damiola, Sylvie Mazoyer, Olga M Sinilnikova, Christopher A Maxwell, Joseph Vijai, Mark Robson, Noah Kauff, Marina J Corines, Danylko Villano, Julie Cunningham, Adam Lee, Noralane Lindor, Conxi Lázaro, Douglas F Easton, Kenneth Offit, Georgia Chenevix-Trench, Fergus J Couch, Antonis C Antoniou, Miguel Angel Pujana (2015)Assessing associations between the AURKA-HMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers, In: PloS one10(4)0120020pp. e0120020-e0120020

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04-1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03-1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted pinteraction values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.