Evaluation of promoter hypermethylation of tumor suppressor gene BRCA1 in epithelial ovarian cancer.

Abstract

Epithelial ovarian cancer (EOC) is a serious gynecological issue worldwide and its late detection is the major encumbrance in treatment procedures. Hypermethylation-mediated BRCA1 gene silencing results in failure of the repair system of damaged DNA playing an important role in ovarian carcinogenesis. BRCA1 gene hypermethylation can serve as a safe and highly specific clinical marker for EOC. The present study was conducted to evaluate the promoter hypermethylation of BRCA1 gene in EOC patients. This hospital-based case-control study carried out in the tertiary care hospital in New Delhi. Subjects and Methods: Promoter hypermethylation of BRCA1 gene was examined in 30 EOC diagnosed untreated cases confirmed by histopathological examinations and compared with 30 normal healthy controls matched for age using methylation specific-polymerase chain reaction. We found significantly higher BRCA1 promoter hypermethylation in the serum of EOC cases as compared to controls with P < 0.0001. BRCA1 gene methylation was found to have 70% sensitivity for the diagnosis of EOC with 100% specificity. A significant difference was observed in the range of CA125 levels, B12 and Folate levels between EOC cases and controls. We conclude that BRCA1 gene is significantly hypermethylated in EOC patients and thus can prove to be a noninvasive diagnostic tool. Our results provide prefatory evidence that epithelial ovarian epigenome can be influenced by dietary nutrients.