Age at diagnosis of cancer in 185delAG BRCA1 mutation carriers of diverse ethnicities: tentative evidence for modifier factors

Yael Laitman, Rachel Michaelson-Cohen, Rakefet Chen-Shtoyerman, Yael Goldberg, Orit Reish, Rinat Bernstein-Molho, Ephrat Levy-Lahad, Noa Ephrat Ben Baruch, Inbal Kedar, D. Gareth Evans, Sara Haim, Shani Paluch-Shimon, Eitan Friedman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Germline pathogenic sequence variants (PSVs) in BRCA1 substantially increase risk for developing breast (BC) and ovarian cancer (OvC). Yet, incomplete penetrance suggests that modifier factors affect phenotypic expression of mutant BRCA1 alleles. Analysis of identical BRCA1 PSV carriers of diverse ethnicities may provide further evidence for modifier factors. Female carriers of the 185delAG BRCA1 PSV identified through high-risk clinics in Israel, and Manchester England from 1998-2018 were eligible. Data were retrieved from patients records and confirmed (in Israel) by cross referencing with the Israeli National Cancer Registry. Overall, 2503 female carriers were included: 1715 (71.4%) Ashkenazi Jews (AJ), 201 (8.3%) Iraqi Jews and 383 (15.9%) of mixed ethnicity. In 102 (4.2%) cases ethnicity could not be ascertained. Of Israeli AJ carriers 649 (37.8%), 256 (14.9%) and 62 (3.6%) were diagnosed with BC, OvC or both cancers, respectively. For the Iraqi Jews these frequencies were 76 (37.8%), 43 (21.4%), and 8 (3.98%), respectively. Age at diagnosis of BC in AJ and Iraqi Jews was 46.7 ± 12.3 years and 52.8 ± 12.2 years, respectively (p = 0.001). For OvC age at diagnosis for AJ was 53.5 ± 10.7 years and for Iraqi Jews 50.1 ± 8.8 years (p = 0.0027). No differences in these parameters were noted between English Jews (n = 110) and non-Jews (n = 32). Age at diagnosis of BC and OvC differs between AJ and Iraqi Jews who carry an identical BRCA1 PSV. This finding supports the existence of modifier factors that may be ethnic specific.

Original languageEnglish
Pages (from-to)189-194
Number of pages6
JournalFamilial Cancer
Issue number3
StatePublished - Jul 2021


FundersFunder number
Manchester Biomedical Research CentreIS-BRC-1215–20007
Israel Cancer Association


    • Age at cancer diagnosis
    • BRCA1 germline pathogenic sequence variants
    • Incomplete penetrance
    • Modifier factors


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