Published in:
01-01-2016 | Clinical Trial
Screening for germline mutations in breast/ovarian cancer susceptibility genes in high-risk families in Israel
Authors:
Tamar Yablonski-Peretz, Shani Paluch-Shimon, Lior Soussan Gutman, Yulia Kaplan, Addie Dvir, Inbal Barnes-Kedar, Luna Kadouri, Valeriya Semenisty, Noa Efrat, Victoria Neiman, Yafit Glasser, Rachel Michaelson-Cohen, Lior Katz, Bella Kaufman, Talia Golan, Orit Reish, Ayala Hubert, Tamar Safra, Yuval Yaron, Eitan Friedman
Published in:
Breast Cancer Research and Treatment
|
Issue 1/2016
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Abstract
We evaluated the clinical utility of screening for mutations in 34 breast/ovarian cancer susceptibility genes in high-risk families in Israel. Participants were recruited from 12, 2012 to 6, 2015 from 8 medical centers. All participants had high breast/ovarian cancer risk based on personal and family history. Genotyping was performed with the InVitae™ platform. The study was approved by the ethics committees of the participating centers; all participants gave a written informed consent before entering the study. Overall, 282 individuals participated in the study: 149 (53 %) of Ashkenazi descent, 80 (28 %) Jewish non-Ashkenazi descent, 22 (8 %) of mixed Ashkenazi/non-Ashkenazi origin, 21 (7 %) were non-Jewish Caucasians, and the remaining patients (n = 10–3.5 %) were of Christian Arabs/Druze/unknown ethnicity. For breast cancer patients (n = 165), the median (range) age at diagnosis was 46 (22–90) years and for ovarian cancer (n = 15) 54 (38–69) years. Overall, 30 cases (10.6 %) were found to carry a pathogenic actionable mutation in the tested genes: 10 BRCA1 (3 non-founder mutations), 9 BRCA2 (8 non-founder mutations), and one each in the RAD51C and CHEK2 genes. Furthermore, actionable mutations were detected in 9 more cases in 4 additional genes (MSH2, RET, MSH6, and APC). No pathogenic mutations were detected in the other genotyped genes. In this high-risk population, 10.6 % harbored an actionable pathogenic mutation, including non-founder mutations in BRCA1/2 and in additional cancer susceptibility genes, suggesting that high-risk families should be genotyped and be assigned a genotype-based cancer risk.