Association of BRCA1 promoter methylation with rs11655505 (c.2265C>T) variants and decreased gene expression in sporadic breast cancer

Breast cancer is the most common cancer and the main cause of cancer morbidity for women worldwide and is manifestation of abnormal genetic as well as epigenetic changes. Therefore, our aim was to study the association of BRCA1 promoter methylation with rs11655505 (c.-2265C/T) variants and gene expression in sporadic breast cancer. Twenty-nine sporadic breast cancer tissues and 26 normal biopsies were used for this study. Genomic DNA and total RNA were extracted from paraffin-embedded tissue and SNP analysis performed. Methylation status of the BRCA1 promoter region was determined by methylation-specific PCR after sodium bisulfite modification of DNA. Among all clinical-pathological parameters only estrogen receptor -ve and +ve samples were significantly different for methylation status (P = 0.04). The genotypic (CC, CT and TT), allelic frequencies and methylation status had not been found to be significantly different from that of healthy controls (P = 0.67, 0.71 and 0.17, respectively). Similarly, methylated BRCA1 promoter was not found to be significantly different in different genotypes from unmethylated promoters between patients and controls. Interestingly, only heterozygous (CT) genotypes with low and normal expression of BRCA1 were significantly different for the differential expression of BRCA1 compared to controls (P = 0.004). However, in tumor samples decreased expression of gene is associated with methylated state of BRCA1 promoter [OR (95 % CI) = 25.09 (2.17-29.75); P = 0.01]. Our data suggest that both single nucleotide variations rs11655505 (c.-2265C/T) and the methylation status of BRCA1 are not associated significantly with the occurrence of sporadic breast cancer in studied population. However, decreased expression of gene is associated with the CT genotypes and the disease. But, in case of tumor samples, an association of methylation of the promoter to the decreased expression of BRCA1 gene suggests the possible role of methylation in gene silencing.