Population-basedBRCA1/2testing programmes are highly acceptable in the Jewish community: results of the JeneScreen Study

Abstract

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.

Clinical Significance of Brca1 Gene Sequencing and Its Promoter Methylation Testing in the Search Strategy for Therapeutic Targets in Breast Cancer Treatment

“…For example, the 185delAG and 5382insC mutations in the BRCA1 gene and the 6174delT mutation in the BRCA2 gene are found with an increased frequency among Ashkenazi Jews. In this population group, those three mutations account for more than 90% of all mutations detected in the BRCA1/2 genes [10]. In Italy, in the region of Tuscany, more than 73% of all detec ted mutations in the BRCA1 gene are the 3347delAG, 3404delA, 1499insA, and 5181del-GTT mutations [11].…”

Screening and prevention of ovarian cancer

“…The largest evidence base for population testing currently comes from BRCA testing studies in the Jewish population. Jewish population‐based BRCA testing more than doubles the number of BRCA carriers identified; is safe, feasible and acceptable; has high satisfaction; reduces anxiety; does not detrimentally affect quality of life or lifestyle; and is cost‐saving for the health system 58,66‐69 . As a result, population‐based BRCA testing was introduced in Israel in 2022 70 and was recently launched as a pilot National Health Service program for the UK Jewish population in February 2023 71…”