BRCA Screening and Identification of a Common Haplotype in the Jewish Community of Rome Reveal a Founder Effect for the c.7007G>C, p. (Arg2336Pro) BRCA2 Variant

TL;DR

This study identifies a common BRCA2 mutation in the Jewish community of Rome, suggesting a founder effect and highlighting the need for targeted genetic screening.

Contribution

The study is the first to identify a founder effect for the BRCA2 c.7007G>C variant in the Jewish community of Rome.

Findings

26.5% of probands from the Jewish community of Rome carried the BRCA2 c.7007G>C pathogenic variant.

Haplotype analysis revealed a shared genetic segment among carriers, indicating a founder effect.

The haplotype length suggests the Roman Jewish community may be the oldest in Europe.

Abstract

Ethnical minorities can present higher rates of cancer susceptibility variants with a founder effect. This is the first study on BRCA1/2 analysis in breast and ovarian cancer cases in the Jewish community of Rome. A significant portion of probands with breast/ovarian cancer from the Jewish community of Rome harbored the heterozygous BRCA2 c.7007G>C pathogenic variant. Haplotype analysis suggested a founder effect with remote origin.

Background/Objectives: Cancer risk-reducing strategies in Ashkenazi women carrying founder variants have a cost-effective effect on reducing cancer morbidity and mortality. The British and US guidelines recommend BRCA1/2 (BRCA) screening among Ashkenazi Jewish people to identify high-risk individuals. BRCA status has not been investigated yet in the Jewish community of Rome. Methods: Patients were selected from the Family Cancer Clinic of the Umberto I University Hospital of Rome, and 38 unrelated families (28 of Roman Jewish and 10 of Libyan Jewish origin) were enrolled, comprising 44 subjects diagnosed with breast and/or ovarian cancer. Genetic counseling and germline BRCA testing were conducted. Haplotype analysis was performed. Results: Of the probands, 26.5% (9/34) from 7/28 unrelated families (25%) in the Jewish community of Rome harbored the known BRCA2 c.7007G>C, p. (Arg2336Pro) variant (rs28897743). Genetic analysis of the four unrelated carriers revealed a shared haplotype, indicating a potential founder effect. The length of the haplotype might confirm the Roman community to be the oldest among Jewish communities in Europe. Conclusions: This study indicates the BRCA2 c.7007G>C variant found in the Jewish community of Rome to be a founder variant. Finally, we underline a pressing need to address the increased risk of carrying BRCA mutations among individuals with Jewish heritage, and to enhance genetic counseling and screening efforts in ethnic minorities that are not otherwise routinely reached.

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