Recurrent Mutations in BRCA1, BRCA2, RAD51C, PALB2 and CHEK2 in Polish Patients with Ovarian Cancer

SIMPLE SUMMARY: In Poland, ovarian cancer is the fourth leading cause of death from cancer among women. Several founder mutations in the BRCA1, BRCA2, PALB2, RAD51C, and CHEK2 genes are associated with breast and ovarian cancer. The aim of the study was to analyze the frequency and magnitude of association of 21 recurrent founder germline mutations in the above genes with ovarian cancer risk among unselected patients in Poland. The ovarian cancer risk was associated with mutations in BRCA1, BRCA2, RAD51C, and PALB2 but not in the CHEK2 gene. Excluding CHEK2, pathogenic mutations in the other 18 alleles were present in 12.5% of cases and 0.6% of healthy controls. A mutation was found in 25.8% of familial cases vs. 9.9% of non-familial cases. We recommend that in Poland all women with ovarian cancer and first-degree female relatives should be tested for the panel of 18 founder mutations in BRCA1, BRCA2, PALB2, and RAD51C. ABSTRACT: The aim of the study was to analyze the frequency and magnitude of association of 21 recurrent founder germline mutations in BRCA1, BRCA2, PALB2, RAD51C, and CHEK2 genes with ovarian cancer risk among unselected patients in Poland. We genotyped 21 recurrent germline mutations in BRCA1 (9 mutations), BRCA2 (4 mutations), RAD51C (3 mutations), PALB2 (2 mutations), and CHEK2 (3 mutations) among 2270 Polish ovarian cancer patients and 1743 healthy controls, and assessed the odds ratios (OR) for developing ovarian cancer for each gene. Mutations were detected in 369 out of 2095 (17.6%) unselected ovarian cancer cases and 117 out of 1743 (6.7%) unaffected controls. The ovarian cancer risk was associated with mutations in BRCA1 (OR = 40.79, 95% CI: 18.67–114.78; p = 0.29 × 10(−15)), in BRCA2 (OR = 25.98; 95% CI: 1.55–434.8; p = 0.001), in RAD51C (OR = 6.28; 95% CI 1.77–39.9; p = 0.02), and in PALB2 (OR 3.34; 95% CI: 1.06–14.68; p = 0.06). There was no association found for CHEK2. We found that pathogenic mutations in BRCA1, BRCA2, RAD51C or PALB2 are responsible for 12.5% of unselected cases of ovarian cancer. We recommend that all women with ovarian cancer in Poland and first-degree female relatives should be tested for this panel of 18 mutations.