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2022-RA-1465-ESGO Randomised trial of population based BRCA testing in Ashkenazi Jews: long term secondary lifestyle behavioural outcomes
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  1. Matthew Burnell1,
  2. Faiza Gaba2,
  3. Michail Sideris3,
  4. Monika Sobocan3,
  5. Rakshit Rakshit2,
  6. Saskia Sanderson4,
  7. Kelly Loggenberg5,
  8. Sue Gessler6,
  9. Lucy Side7,
  10. Angela Brady8,
  11. Huw Dorkins9,
  12. Yvonne Wallis10,
  13. Chris Jacobs11,
  14. Rosa Legood12,
  15. Uziel Beller13,
  16. Ian Tomlinson14,
  17. Jane Wardle4,
  18. Usha Menon2,
  19. Ian Jacobs15 and
  20. Ranjit Manchanda3
  1. 1MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK
  2. 2Department of Gynaecological Oncology, Barts Health NHS Trust, London, UK
  3. 3Wolfson Institute of Population Health, Barts CRUK Cancer Centre, Queen Mary University of London, London, UK
  4. 4Behavioral Sciences Unit, Department of Epidemiology and Public Health, University College London, London, UK
  5. 5Department of Clinical Genetics, North East Thames Regional Genetics Unit, Great Ormond Street Hospital, London, UK
  6. 6University College London, Department of Gynaecological Oncology, Institute, UK
  7. 7University Hospital Southampton NHS Foundation Trust, Southampton, UK
  8. 8Dept Clinical Genetics, North West Thames Regional Genetics Unit, Northwick Park Hospital, London, UK
  9. 9St Peter’s College, University of Oxford, Oxford, UK
  10. 10West Midlands Regional Genetics Laboratory, Birmingham Women’s NHS Foundation Trust, Birmingham, UK
  11. 11Department of Clinical Genetics, Guy’s Hospital, London, UK
  12. 12Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK
  13. 13Department of Gynaecology, Shaare Zedek Medical Center, Jerusalem, Israel
  14. 14Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK
  15. 15University of New South Wales, Sydney, Australia

Abstract

Introduction/Background Ashkenazi-Jewish (AJ) population-based BRCA-testing is acceptable, does not detrimentally impact psychological well-being or quality of life, is cost-effective and amplifies primary prevention for breast cancer (BC) ovarian cancer (OC). However, prospective data describing lifestyle impact are lacking. We report long-term results of a population-based BRCA-testing randomised controlled trial (RCT) on lifestyle behaviour and cancer-risk perception.

Methodology We designed a two-arm RCT (ISRCTN-73338115, GCaPPS): (a)Population-Screening (PS) arm; (b) family-history (FH)/Clinical-criteria testing arm. Women and men >18-years in the North-London AJ-population were offered informed pre-test genetic counselling and BRCA testing. Participants were recruited through self-referral. Exclusions included: prior BRCA-testing or first-degree relatives of BRCA-carriers. 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 customised/validated questionnaires at baseline/1-year/2-years/3-years follow-up. Outcome measures included lifestyle/behavioural outcomes. Generalized linear-mixed models adjusted for covariates and appropriate contrast-tests were used for between-group and within-group analysis of lifestyle and behavioural outcomes along-with evaluating factors associated with these outcomes. Outcomes are adjusted for multiple testing (Bonferoni method), with p<0.0039 considered significant.

Results 1034 participants were randomized to PS (n=530) or FH (n=504) arms. No significant difference was identified between PS and FH-based BRCA-testing approaches for 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. The risk was found to be lowest in BRCA-negative participants. Men consume fewer fruits, vegetables and vitamins but more meat and alcohol than women (p<0.001).

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

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