Randomised trial of population-based BRCA testing in Ashkenazi Jews: long-term secondary lifestyle behavioural outcomes.

Huw Dorkins, Ranjit Manchanda, Ian Jacobs, Usha Menon, Jane Wardle, Ian Tomlinson, Uziel Beller, Rosa Legood, Chris Jacobs, Yvonne Wallis, Matthew Burnell, Angela F Brady, Lucy Side, Sue Gessler, Kelly Loggenberg, Saskia Sanderson, Rakshit Desai, Monika Sobocan, Faiza Gaba

Journal: BJOG : an international journal of obstetrics and gynaecology 2022;129(12):1970-1980

PMID: 35781768

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Abstract

OBJECTIVE

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.

DESIGN

Two-arm randomised controlled trials (ISRCTN73338115, GCaPPS): (a) population-screening (PS); (b) family history (FH)/clinical criteria testing.

SETTING

North London AJ-population.

POPULATION/SAMPLE

AJ women/men >18 years.

EXCLUSIONS

prior BRCA testing or first-degree relatives of BRCA-carriers.

METHODS

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 < 0.0039 considered significant.

OUTCOME MEASURES

Lifestyle/behavioural outcomes at baseline/1-year/2-year/3-year follow-ups.

RESULTS

1034 participants were randomised to PS (n = 530) or FH (n = 504) arms. No significant difference was identified between PS- and FH-based BRCA testing approaches in terms of dietary fruit/vegetable/meat consumption, vitamin intake, alcohol quantity/ frequency, smoking behaviour (frequency/cessation), physical activity/exercise or routine breast mammogram screening behaviour, with outcomes not affected by BRCA test result. Cancer risk perception decreased with time following BRCA testing, with no difference between FH/PS approaches, and the perception of risk was lowest in BRCA-negative participants. Men consumed fewer fruits/vegetables/vitamins and more meat/alcohol than women (P < 0.001).

CONCLUSION

Population-based and FH-based AJ BRCA testing have similar long-term lifestyle impacts on smoking, alcohol, dietary fruit/vegetable/meat/vitamin, exercise, breast screening participation and reduced cancer risk perception.

Address: MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK.; Wolfson Institute of Population Health, Barts CRUK Cancer Centre, Queen Mary University of London, London, UK.; Department of Gynaecological Oncology, Barts Health NH Trust, London, UK.; Behavioural Sciences Unit, Department Epidemiology and Public Health, University College London, London, UK.; Department Clinical Genetics, North East Thames Regional Genetics Unit, Great Ormond Street Hospital, London, UK.; Department of Gynaecological Oncology, Institute for Women's Health, University College London, London, UK.; University Hospital Southampton NHS Foundation Trust, Southampton, UK.; Department Clinical Genetics, North West Thames Regional Genetics Unit, Northwick Park Hospital, London, UK.; St Peter's College, University of Oxford, Oxford, UK.; West Midlands Regional Genetics Laboratory, Birmingham Women's NHS Foundation Trust, Birmingham, UK.; Depatment Clinical Genetics, West Midlands Regional Genetics Service, Birmingham Women's NHS Foundation Trust, Birmingham, UK.; Depatment Clinical Genetics, Guy's Hospital, London, UK.; University of Technology Sydney, Sydney, New South Wales, Australia.; Department of Health Services Research and Policy, London School of Hygiene & Tropical Medicine, London, UK.; Department of Gynaecology, Shaare Zedek Medical Center, Jerusalem, Israel.; Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.; University of New South Wales, Sydney, New South Wales, Australia.; Department of Gynaecology, All India Institute of Medical Sciences, New Delhi, India.

DOI: 10.1111/1471-0528.17253

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MeSH Terms: Adult, Breast Neoplasms, Female, Genetic Predisposition to Disease, Genetic Testing, Humans, Jews, Life Style, Male, Ovarian Neoplasms, Vitamins