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

BJOG. 2020 Feb;127(3):364-375. doi: 10.1111/1471-0528.15905. Epub 2019 Sep 10.


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.

Keywords: BRCA1; BRCA2; Ashkenazi Jews; genetic testing; population testing; psychological; quality-of-life.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anxiety* / physiopathology
  • Anxiety* / prevention & control
  • Early Detection of Cancer* / methods
  • Early Detection of Cancer* / psychology
  • Female
  • Genes, BRCA1*
  • Genes, BRCA2*
  • Genetic Predisposition to Disease / psychology
  • Genetic Testing / methods
  • Genetic Testing / statistics & numerical data
  • Hereditary Breast and Ovarian Cancer Syndrome* / diagnosis
  • Hereditary Breast and Ovarian Cancer Syndrome* / ethnology
  • Hereditary Breast and Ovarian Cancer Syndrome* / genetics
  • Hereditary Breast and Ovarian Cancer Syndrome* / psychology
  • Humans
  • Jews / genetics
  • Jews / statistics & numerical data
  • London / epidemiology
  • Male
  • Medical History Taking / statistics & numerical data
  • Quality of Life*
  • Uncertainty