Epigenetic silencing of BRCA1 gene associated with demographic and pathologic factors in sporadic breast cancer: a study of an Indian population.

Breast cancer (BC) is a leading cause of cancer-related deaths among women worldwide, and this study further demonstrates that the women of Varanasi (north India) are not untouched by this fatal disease. During BC development, epigenetic activity plays a key role in silencing gene expression. Its widespread occurrence in the cancer genome could inactivate many cellular pathways including DNA repair, cell cycle control, apoptosis, cell adherence, and detoxification. In this study, our aim was to determine the penetrance of BRCA1 promoter methylation and its correlation with pathological and demographic factors in sporadic BC in an Indian population. Our analysis included 127 patients who were diagnosed with sporadic BC. Methylation-specific PCR for the BRCA1 promoter was used during the study and correlated with pathological and demographic factors. Methylation of the BRCA1 promoter was detected in 8.7% (11/127) of the tumors. Correlation of promoter methylation with demographic factors and clinicopathological markers revealed the following data: (i) BRCA1 methylation was more frequently observed in tumor samples taken from premenopausal or perimenopausal women (P=0.026), (ii) methylation of the BRCA1 promoter negatively correlated with estrogen receptor (P=0.040), progesterone receptor (P=0.013), and epidermal growth factor receptor-2 (P=0.002), (iii) the overall promoter methylation was higher in more advanced stages (P=0.036) of the disease. This study has immense implications for understanding epigenetic mechanisms in BC development. The result suggests that the epigenetic silencing of BRCA1 is uncommon and is associated with the triple-negative phenotype.