Association Between WRN Cys1367Arg (T>C) and Cancer Risk

Abstract

Growing evidence suggests that aberration of the DNA repair pathway significantly contributes to tumorigenesis. Single-nucleotide polymorphisms in DNA repair-related genes such as WRN have been implicated in cancer risk. However, the results of published studies remain inconclusive. Therefore, we performed a meta-analysis of all available and relevant published studies to clarify the role of this polymorphism in cancer. We performed a computerized search of PubMed for publications on WRN Cys1367Arg (T>C) polymorphism and cancer risk and analyzed the genotype data. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. Sensitivity analysis, heterogeneity test, cumulative meta-analysis, and bias assessment were performed using STATA software 11.0. No association was found between WRN Cys1367Arg (T>C) polymorphism and cancer risk in all genetic models. When stratified by cancer type, results showed that this polymorphism increased the risk of breast cancer (2CC+CT vs 2TT+CT: perallele OR = 1.14, 95% CI = 1.03-1.26, Ptrend = .012; CC vs TT: OR = 1.43, 95% CI = 1.04-1.95, Pvalue = .026; CC+CT vs TT: OR = 1.14, 95% CI = 1.02-1.28, Pvalue = .027). In another analysis stratified by ethnicity, WRN Cys1367Arg (T>C) polymorphism was significantly associated with cancer susceptibility in Europeans (2CC+CT vs 2TT+CT: perallele OR = 1.09, 95% CI = 1.00-1.19, Ptrend = .042; CT vs TT: OR = 1.13, 95% CI = 1.01-1.27, Pvalue = .032; and CC+CT vs TT: OR = 1.13, 95% CI = 1.02-1.26, Pvalue = .025). Our study suggests that WRN Cys1367Arg (T>C) polymorphism is not associated with overall cancer risk, although subgroup analyses suggested an association with breast cancer and overall cancer specifically in European populations.