Clinical signiifcance of BRCA1, GSTP1 and MGMT gene methylation status in breast cancer / 中国癌症杂志

ABSTRACT

Background and purpose: DNA methylation is an important mechanism for regulating gene expression, and plays an important role in the tumorigenesis. Study shows that DNA methylation is a potentially promising biomarker in tumor diagnosis, prognosis as well as treatment selection. This study aimed to analyze the methylation status and assessed possible clinical value of 3 DNA repair genes BRCA1, GSTP1 and MGMT in breast cancer samples of Chinese women. Methods:Using methylation speciifc PCR (MSP), we analyzed the methylation status of 3 DNA repair genes BRCA1, GSTP1 and MGMT in 106 paired breast tumors and corresponding normal tissues. Results: The methylation rates of BRCA1, GSTP1 and MGMT were 24.5% (26/106), 29.2% (31/106) and 18.9%(20/106) in breast cancer tissues, which were higher than those (7.5%, 11.3%and 4.7%) in paired normal breast tissues, respectively (P<0.01). Methylation in at least one of the genes was found in 50.9%(54/106) of the breast cancer and 19.8%(21/106) in paired normal breast tissues. And the mean number of genes hypermethylated in each tumor and paired normal breast tissues were 0.73 and 0.24, respectively (P<0.000 1). The methylation status of BRCA1 was more frequent in the younger patients than in the older patients (P=0.007) and most BRCA1 methylated patients were ER negative (P=0.020). Methylation status of GSTP1 was signiifcantly correlated with tumor size, lymph node metastasis (P=0.028 and 0.033, respectively). MGMT methylation was significantly correlated with tumor stage, higher tumor grade and lymph node metastasis (P=0.016, 0.025 and 0.030, respectively). High frequency simultaneous methylation of these 3 genes was more often in those with higher tumor stage and lymph node metastasis (P=0.028 and 0.007, respectively). Conclusion:Hypermethylation of BRCA1, GSTP1 and MGMT genes may be linked to various known clinicopathological features of breast cancer in Chinese women, and the increasing multiple gene methylation in tumors may indicate an aggressive phenotype for breast cancer. Detection of the methylation status of these genes may be useful for identifying patients at high risk for breast cancer.