title: Aberrant promoter methylation of cancer-related genes in human breast cancer.
abstract: The clinical relevance of aberrant DNA methylation is being increasingly recognized in breast cancer. The present study aimed to evaluate the promoter methylation status of seven candidate genes and to explore their potential use as a biomarker for the diagnosis of breast cancer. A total of 70 Chinese patients with breast cancer were recruited, and matched with 20 patients with benign breast disease (BBD). Methylation-specific polymerase chain reaction was performed to measure the methylation status of selected genes. The protein expression of candidate genes was determined by immunohistochemistry. Hypermethylation of Breast cancer 1, early onset; DNA repair associated (BRCA1), glutathione S-transferase pi 1 (GSTP1), cyclin dependent kinase inhibitor 2A, O-6-methylguanine-DNA methyltransferase, phosphatase and tensin homolog, retinoic acid receptor beta 2 and cyclin D2 was observed to be more common in cancerous tissues (24.3, 31.4, 40.0, 27.1, 48.6, 55.7 and 67.1%, respectively) as compared with BBD controls (0.0, 0.0, 20.0, 25.0, 40.0, 40.0 and 45.0%, respectively). Immunohistochemical analysis demonstrated a correlation between the methylation of the target gene and downregulation of protein expression. When BRCA1 and GSTP1 were combined as the biomarker, the area under the receiver operating characteristic curve reached 0.721 (95% confidence interval, 0.616-0.827). The present findings indicated that promoter methylation of cancer-related genes was frequently observed in patients with breast cancer and was associated with various clinical features. Hypermethylation of BRCA1 and GSTP1 may be used as promising biomarkers for breast cancer.
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Gastrointestinal Surgery, Aoyoung Hospital, Zhangjiagang, Jiangsu 215617, P.R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.
authors.forename: Xianzhen
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.
authors.forename: Simin
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.
authors.forename: Guisheng
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.
authors.forename: Xianzhi
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China; Department of Social Medicine and Health Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, P.R. China; The Innovation Center for Social Risk Governance in Health, Nanjing, Jiangsu, 211166, P.R. China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Breast, Nanjing Maternity and Child Health Hospital of Nanjing Medical University, Nanjing, Jiangsu 210004, P.R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Lu
keywords: benign breast disease; breast cancer; diagnosis; hypermethylation; molecular epidemiology