Randomised trial of population-based BRCA testing in Ashkenazi Jews: long-term outcomes

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

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


Objective: 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. Design: Randomised controlled trial (RCT) (ISRCTN73338115) GCaPPS, with two-arms: (i) population-screening (PS); (ii) FH/clinical-criteria-based testing. Setting: North London Ashkenazi-Jewish (AJ) population. Population/Sample: AJ women/men. Methods: Population-based RCT (1:1). Participants were recruited through self-referral, following pre-test genetic counselling from the North London AJ population. Inclusion criteria: AJ women/men >18 years old; exclusion-criteria: prior BRCA testing or first-degree relatives of BRCA-carriers. Interventions: 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. Main outcome measures: 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. Results: 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 < 0.0005) and quality-of-life (P = 0.004) scores in both PS and FH groups over time. Eighteen of 30 (60%) BRCA carriers identified did not fulfil clinical criteria for BRCA testing. Total BRCA prevalence was 2.9% (95% CI 1.97–4.12%), BRCA1 prevalence was 1.55% (95% CI 0.89–2.5%) and BRCA2 prevalence was 1.35% (95% CI 0.74–2.26%). Conclusion: Population-based AJ BRCA testing does not adversely affect long-term psychological wellbeing or quality-of-life, decreases anxiety and could identify up to 150% additional BRCA carriers. Tweetable abstract: Population BRCA testing in Ashkenazi Jews reduces anxiety and does not adversely affect psychological health or quality of life.

Original languageEnglish
Pages (from-to)364-375
Number of pages12
JournalBJOG: An International Journal of Obstetrics and Gynaecology
Issue number3
StatePublished - 1 Feb 2020
Externally publishedYes


  • Ashkenazi Jews
  • BRCA1
  • BRCA2
  • genetic testing
  • population testing
  • psychological
  • quality-of-life


Dive into the research topics of 'Randomised trial of population-based BRCA testing in Ashkenazi Jews: long-term outcomes'. Together they form a unique fingerprint.

Cite this