Zhou Li-Ping, Luan Hong, Dong Xi-Hua, Jin Guo-Jiang, Man Dong-Liang, Shang Hong
Department of Laboratory Medicine, the First Affiliated Hospital of China Medical University, Shenyang, China.
Asian Pac J Cancer Prev. 2012;13(7):3417-22. doi: 10.7314/apjcp.2012.13.7.3417.
Non-homologous end joining (NHEJ) is one of the pathways of repair of DNA double-strand breaks. A number of genes involved in NHEJ have been implicated as breast cancer susceptibility genes such as LIG4. However, some studies have generated conflicting results. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to investigate association between LIG4 gene polymorphisms in the NHEJ pathway and breast cancer risk.
Studies focusing on the relationship between LIG4 gene polymorphisms and susceptibility to breast cancer were selected from the Pubmed, Cochrane library, Embase, Web of Science, Springerlink, CNKI and CBM databases. Data were extracted by two independent reviewers and the meta-analysis was performed with Review Manager Version 5.1.6 and STATA Version 12.0 software, calculating odds ratios (ORs) with 95% confidence intervals (95%CIs).
According to the inclusion criteria, we final included seven studies with a total of 10,321 breast cancer cases and 10,160 healthy controls in the meta-analysis. The results showed no association between LIG4 gene polymorphisms (rs1805386 T>C, rs1805389 C>T, rs1805388 C>T and rs2232641 A>G) and breast cancer risk, suggesting that the mutant situation of these SNPs neither increased nor decreased the risk for breast cancer. In the subgroup analysis by Hardy-Weinberg equilibrium (HWE) and ethnicity, we also found no associations between the variants of LIG4 gene and breast cancer risk among HWE, non-HWE, Caucasians, Asians and Africans.
This meta-analysis suggests that there is a lack of any association between LIG4 gene polymorphisms and the risk of breast cancer.
非同源末端连接（NHEJ）是DNA双链断裂修复途径之一。一些参与NHEJ的基因已被认为是乳腺癌易感基因，如LIG4。然而，一些研究得出了相互矛盾的结果。本人类基因组流行病学（HuGE）综述和荟萃分析的目的是研究NHEJ途径中LIG4基因多态性与乳腺癌风险之间的关联。
从PubMed、Cochrane图书馆、Embase、科学网、Springerlink、中国知网和中国生物医学文献数据库中筛选关注LIG4基因多态性与乳腺癌易感性关系的研究。由两名独立的评审员提取数据，并使用Review Manager 5.1.6版和STATA 12.0版软件进行荟萃分析，计算比值比（OR）及95%置信区间（95%CI）。
根据纳入标准，我们最终在荟萃分析中纳入了7项研究，共10321例乳腺癌病例和10160例健康对照。结果显示，LIG4基因多态性（rs1805386 T>C、rs1805389 C>T、rs1805388 C>T和rs2232641 A>G）与乳腺癌风险之间无关联，表明这些单核苷酸多态性的突变情况既未增加也未降低患乳腺癌的风险。在按哈迪-温伯格平衡（HWE）和种族进行的亚组分析中，我们还发现HWE、非HWE、白种人、亚洲人和非洲人中LIG4基因变异与乳腺癌风险之间均无关联。
这项荟萃分析表明，LIG4基因多态性与乳腺癌风险之间不存在任何关联。
