title: Promoter methylation of BRCA1 in the prognosis of breast cancer: a meta-analysis.
abstract: The inactivation of BRCA1 by epigenetic alterations is a critical event in breast tumorigenesis, which may potentially be used as a prognostic marker for patients with breast cancer. The present study systematically reviewed the promoter methylation of BRCA1 and its relationship to the clinical outcomes of breast cancer patients. We performed a meta-analysis following the PRISMA guideline. Relevant articles were identified by searching PubMed, Web of Science and Embase database until August 2013. The pooled hazard ratio (HR) and 95 % confidence interval (CI) were applied to estimate the effect of BRCA1 methylation. Random or fixed effect model was chosen based on the heterogeneity analysis. A total of 3,205 patients from nine eligible studies were included in the meta-analysis. BRCA1 methylation was found to be significantly correlated with a poor overall survival of breast cancer, with the combined HR (95 % CI) of 2.02 (1.35-3.03). After adjusting for potential confounders using the Cox regression model, the pooled HR (95 % CI) of BRCA1 methylation on patients' overall survival was 1.38 (1.04-1.84). If we used the disease-free survival as the outcome, the combined HR (95 % CI) was 2.89 (1.73-4.83) for univariate analysis and 3.92 (95 % CI 1.49-10.32) for multivariate analysis, respectively. Subgroup analysis of specimen types revealed that the pooled HR (95 % CI) for overall survival was 1.48 (1.22-1.81) when using formalin-fixed paraffin-embedded (FFPE) specimen and 1.38 (0.16-11.84) when using fresh frozen tissues. As for the disease-free survival, the pooled HR (95 % CI) was 2.47 (1.33-4.58) when using FFPE specimen and 2.78 (1.47-5.28) when using fresh frozen tissues. As a conclusion, the present meta-analysis provides evidence that BRCA1 methylation is associated with a poor survival of breast cancer patients. Our findings underscore the clinical relevance of aberrant epigenetic alteration as a promising biomarker for the prognosis of human cancers.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wu
authors.forename: Fengliang
authors.initials: F
authors.lastname: Wang
authors.forename: Ruobing
authors.initials: R
authors.lastname: Xu
authors.forename: Simin
authors.initials: S
authors.lastname: Zhang
authors.forename: Xianzhen
authors.initials: X
authors.lastname: Peng
authors.forename: Yan
authors.initials: Y
authors.lastname: Feng
authors.forename: Jianming
authors.initials: J
authors.lastname: Wang
authors.forename: Cheng
authors.initials: C
authors.lastname: Lu
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality*; D019175:DNA Methylation; D005260:Female; D019398:Genes, BRCA1; D006801:Humans; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D017594:Publication Bias