Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
Breast Cancer Res Treat. 2013 Dec;142(3):619-27. doi: 10.1007/s10549-013-2774-9. Epub 2013 Nov 21.
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.
BRCA1 的表观遗传失活是乳腺癌发生的关键事件，可能可作为乳腺癌患者的预后标志物。本研究系统地综述了 BRCA1 的启动子甲基化及其与乳腺癌患者临床结局的关系。我们按照 PRISMA 指南进行了荟萃分析。通过检索 PubMed、Web of Science 和 Embase 数据库，查找截至 2013 年 8 月的相关文章。应用风险比（HR）和 95%置信区间（CI）来评估 BRCA1 甲基化的作用。根据异质性分析，选择随机或固定效应模型。共有 9 项符合条件的研究纳入 3205 例患者进行荟萃分析。结果发现，BRCA1 甲基化与乳腺癌患者总生存不良显著相关，合并 HR（95%CI）为 2.02（1.35-3.03）。使用 Cox 回归模型调整潜在混杂因素后，BRCA1 甲基化对患者总生存的合并 HR（95%CI）为 1.38（1.04-1.84）。如果以无病生存为结局，单因素分析的合并 HR（95%CI）为 2.89（1.73-4.83），多因素分析的合并 HR（95%CI）为 3.92（95%CI 1.49-10.32）。对标本类型的亚组分析显示，总生存的合并 HR（95%CI）为 1.48（1.22-1.81）时采用福尔马林固定石蜡包埋（FFPE）标本，为 1.38（0.16-11.84）时采用新鲜冷冻组织。对于无病生存，FFPE 标本的合并 HR（95%CI）为 2.47（1.33-4.58），新鲜冷冻组织的合并 HR（95%CI）为 2.78（1.47-5.28）。综上所述，本荟萃分析提供了 BRCA1 甲基化与乳腺癌患者生存不良相关的证据。我们的研究结果强调了异常表观遗传改变作为人类癌症预后有前途的生物标志物的临床相关性。
