The hMLH1 promoter polymorphisms and cancer susceptibility in Asian populations: a meta-analysis

Abstract

Background: A variety of studies have evaluated the associations between polymorphisms in the promoter regions of the hMLH1 and cancer risk. However, the results remain inconclusive. To better understand the roles of the hMLH1 polymorphisms and cancer risk, we conducted a comprehensive meta-analysis to investigate the association between the hMLH1 -93G/A and 1151T/A (Val384Asp) polymorphisms and cancer risk in Asian population.

Methods: We performed a meta-analysis by conducting searches of the published studies in Pub Med, CNKI, CBM, ISI web of knowledge and Google scholar search databases. Finally, 12 studies were included into our meta-analysis. Overall and subgroup analyses were performed. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the associations between hMLH1 polymorphisms and cancer risk. Statistical analysis was performed with Review Manager 5.0.

Results: Twelve studies addressing two hMLH1 polymorphisms were analyzed among a total of 4128 cancer cases and 4678 controls. For hMLH1 -93G/A, there was no evidence that the hMLH1 -93G/A polymorphism was significantly associated with an increased cancer risk (P>0.05) in Asian populations (heterozygote comparison: OR=0.89 [95% CI (0.75, 1.060)] P=0.20; dominant model comparison: OR=0.98 [95% CI (0.83, 1.15)] P=0.79). In subgroup analysis based on cancer types and the sources of control, no associations were found in colorectal cancer, gastric cancer and "other cancers" under the any gene model except for lung cancer (recessive model comparison: OR=1.69 [95% CI (1.30, 2.19)] P<0.0001). For hMLH1 1151T/A, the polymorphism significantly associated with an increased cancer risk in Asians: OR=1.88 [95% CI (1.49, 2.25)], P<0.0001, and OR=1.87 [95% CI (1.49, 2.25)], P<0.0001.

Conclusions: Our investigations demonstrated that the hMLH1 -93G/A polymorphism is not a candidate for susceptibility to overall cancers, and that the hMLH1 1151T/A polymorphism is significantly associated with higher cancer risk in Asian populations. Further studies with large sample size for hMLH1 should be conducted.