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01-12-2013 | Epidemiology

Promoter methylation of BRCA1 in the prognosis of breast cancer: a meta-analysis

Authors: Liang Wu, Fengliang Wang, Ruobing Xu, Simin Zhang, Xianzhen Peng, Yan Feng, Jianming Wang, Cheng Lu

Published in: Breast Cancer Research and Treatment | Issue 3/2013

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.

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Title: Promoter methylation of BRCA1 in the prognosis of breast cancer: a meta-analysis
Authors: Liang Wu
Fengliang Wang
Ruobing Xu
Simin Zhang
Xianzhen Peng
Yan Feng
Jianming Wang
Cheng Lu
Publication date: 01-12-2013
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 3/2013
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-013-2774-9

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