A multicenter study of genotype variation/demographic patterns in 2475 individuals inluding with 1444 cases with breast cancer in Turkey Short Title: BRCA profiling of breast-cancer patients in Turkey

Abstract BACKGROUND Breast Cancer is the most common cancer type in women, second among the all cancers, and inherited with autosomal dominant pattern. The clinical diagnosis of BC relies on the published diagnostic criteria, and two genes have been identified as the main causative for breast cancer which are BRCA1 and BRCA2. OBJECTIVE We aimed to compare the index cases with the diagnostic features to describe the genotype/demographic information association in breast cancer. METHODS We performed mutational analyses for the BRCA1 and BRCA2 genes on 2475 individuals from collobrative centers across Turkey, whom 1444 of them were ascertained index cases. RESULTS We identified mutations in 17% (421/2475) of all individuals while its almost the same 16.6% (239/1444) in 1444 index cases. Mutations in BRCA1/BRCA2 genes were detected in 17.8% (131/737) of familial cases and 12% (78/549) of sporadic breast cancer, with 4.9% of mutations in the BRCA1 and 12% in the BRCA2. CONCLUSIONS Genotype variation and demographic information patterns were analyzed of all observed breast cancer findings in probands. We showed that patients with BRCA2 mutations have significantly been identified more than BRCA1 mutations. We also observed that sporadic breast cancer cases without familial history have less mutation positivity in BRCA1/BRCA2 genes, and the results were consistent with other studies in the Mediterranean region. On performing meta-analyses of our data and the other limited studies of the Mediterranean region in the literature, we found significant correlations that individual studies did not have sufficient power to conclude. Correlating genotypes with demographic information should facilitate the disease management of BC both the familial and non-familial cases.