Lack of Association Between LIG4 Gene Polymorphisms and the Risk of Breast Cancer: A HuGE Review and Meta-analysis

Objective: Non-homologous end joining (NHEJ) is one of the pathways of repair of DNA double-strandbreaks. A number of genes involved in NHEJ have been implicated as breast cancer susceptibility genes such asLIG4. 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 NHEJpathway and breast cancer risk.
Methods: Studies focusing on the relationship between LIG4 gene polymorphismsand 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-analysiswas performed with Review Manager Version 5.1.6 and STATA Version 12.0 software, calculating odds ratios(ORs) with 95% confidence intervals (95%CIs).
Results: According to the inclusion criteria, we final includedseven studies with a total of 10,321 breast cancer cases and 10,160 healthy controls in the meta-analysis. Theresults showed no association between LIG4 gene polymorphisms (rs1805386 T>C, rs1805389 C>T, rs1805388C>T and rs2232641 A>G) and breast cancer risk, suggesting that the mutant situation of these SNPs neitherincreased 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 riskamong HWE, non-HWE, Caucasians, Asians and Africans.
Conclusion: This meta-analysis suggests that thereis a lack of any association between LIG4 gene polymorphisms and the risk of breast cancer.