Aberrant GSTP1 promoter methylation is associated with increased risk and advanced stage of breast cancer: a meta-analysis of 19 case-control studies

Cheng Fang, Xue-Mei Wei, Xian-Tao Zeng, Fu-Bing Wang, Hong Weng, Xinghua Long

Glutathione S-transferase P1 (GSTP1) has been reported to function as a tumor suppressor gene in various types of human cancers. Aberrant methylation of tumor-related genes at the promoter regions can inactivate genes, which is important in the carcinogenesis of breast cancer. However, the role of GSTP1 promoter methylation in the occurrence of breast cancer and its relationship with tumor stage and histological grade has not been fully elucidated. Thus, we carried out a meta-analysis to yield a more accurate association. A systematically literature search was made on PubMed, EMBASE and Web of Science databases for eligible studies. The odds ratio (OR) and 95 % confidence interval (95 % CI) were calculated by RevMan 5.2 software. Subgroup and sensitivity analyses were conducted to explore the source of heterogeneity. Eventually, 17 articles involving 19 case-control studies were included in the present meta-analysis. Overall, the pooled results indicated that aberrant GSTP1 promoter methylation was significantly associated with the risk of breast cancer (OR = 7.85, 95 % CI = 5.12-12.01; Caucasians OR = 7.23, 95 % CI = 3.76-13.90 and Asians OR = 11.71, 95 % CI = 5.69-24.07). Furthermore, our results revealed that GSTP1 promoter methylation was more often observed in late-stage breast cancer patients compared with early-stage ones (OR = 1.84, 95 % CI = 1.32-2.58). However, no significant association was identified between GSTP1 promoter methylation and histological grade (OR = 0.74, 95 % CI = 0.43-1.26). The results indicated that GSTP1 promoter methylation probably plays an important role in breast carcinogenesis, which could serve as an effective biomarker for the diagnosis and monitor of breast cancer.