Genotype-phenotype correlations among BRCA1 4153delA and 5382insC mutation carriers from Latvia

We investigated the prevalence of the BRCA1 founder mutations c.4034delA and c.5266dupC in a population-based series of unselected breast (n = 2546) and ovarian (n = 795) cancer cases. Among the BRCA1 mutation carriers identified in this analysis we compared the overall survival, age at diagnosis and family histories of breast and ovarian cancers.We have found that the prevalence of breast and ovarian cancer cases (breast: ovarian cancer ratio) differs significantly among the carriers of the c.5266dupC and c.4034delA founder mutations (OR = 2.98, 95%CI = 1.58 to 5.62, P < 0.001). We have also found a difference in the prevalence of breast and ovarian cancer cases among the 1st and 2nd degree relatives of the c.4034delA and c.5266dupC mutation carriers. In addition, among the breast cancer cases the c.4034delA mutation has been associated with a later age of onset and worse clinical outcomes in comparison with the c.5266dupC mutation.Our data suggest that the carriers of the c.4034delA and c.5266dupC founder mutations have different risks of breast and ovarian cancer development, different age of onset and prognosis of breast cancer.Breast cancer is the most prevalent malignancy and the leading cause of death from cancer among women in Latvia. Ovarian cancer appears less frequent; however, it remains a significant cause of cancer mortality in Latvia and worldwide. Hereditary cancer syndromes account for up to 5-10% of breast cancer cases and for up to 5-15% of ovarian cancer cases [1,2]. Germline mutations of the BRCA1 and BRCA2 genes represent the most significant and thus far the best characterized genetic risk factors for breast and ovarian cancer development [3]. More than 1000 distinct cancer-associated BRCA1 [MIM 113705] mutations have been already described; however, not all of them are equally pathogenic and most probably there is a different cancer risk associated with specific mutations [4]. In sporadic breast carcinoma, BRCA1 is rarely mutated, although ex