Amity Institute of Biotechnology, Amity University, Uttar Pradesh, India.
Eur J Cancer Prev. 2011 Nov;20(6):478-83. doi: 10.1097/CEJ.0b013e32834761a6.
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.
乳腺癌（BC）是全球女性癌症相关死亡的主要原因，本研究进一步表明，瓦拉纳西（印度北部）的女性也无法免受这种致命疾病的影响。在 BC 发展过程中，表观遗传活性在沉默基因表达中起着关键作用。其在癌症基因组中的广泛发生可能会使许多细胞途径失活，包括 DNA 修复、细胞周期控制、细胞凋亡、细胞黏附和解毒。在这项研究中，我们的目的是确定 BRCA1 启动子甲基化的外显率及其与印度人群中散发性 BC 的病理和人口统计学因素的相关性。我们的分析包括 127 名被诊断为散发性 BC 的患者。在研究过程中使用了针对 BRCA1 启动子的甲基化特异性 PCR，并与病理和人口统计学因素相关联。在 8.7%（11/127）的肿瘤中检测到 BRCA1 启动子的甲基化。启动子甲基化与人口统计学因素和临床病理标志物的相关性显示出以下数据：（i）BRCA1 甲基化在绝经前或围绝经期女性的肿瘤样本中更频繁地观察到（P=0.026），（ii）BRCA1 启动子的甲基化与雌激素受体（P=0.040）、孕激素受体（P=0.013）和表皮生长因子受体-2（P=0.002）呈负相关，（iii）疾病更晚期（P=0.036）的总启动子甲基化更高。这项研究对于理解 BC 发展中的表观遗传机制具有重要意义。结果表明，BRCA1 的表观遗传沉默不常见，并且与三阴性表型相关。
