Current evidence on the relationship between SNP309 polymorphism in the MDM2 gene and colorectal cancer risk.

Abstract

It has been demonstrated that MDM2 is a well-established negative regulator of the p53 protein and might be associated with a significantly earlier age of onset of several tumors, including colorectal cancer (CRC). In recent years, a T to G substitution (SNP309) in the promoter of MDM2 has been extensively studied as a potential CRC risk factor; however, the results are inconsistent. To derive a more precise estimation of association between MDM2 SNP309 polymorphism and CRC risk, we conducted a meta-analysis of 11 studies with 4,050 CRC cases and 3,688 controls. For MDM2 SNP309 polymorphism, no obvious associations were found for all genetic models when all studies were pooled into the meta-analysis. In the subgroup analyses by ethnicity, source of controls, and Hardy-Weinberg equilibrium (HWE) in controls, a significantly increased risk was observed among Asians (heterozygous model: odds ratio (OR) = 1.21, 95% confidence interval (CI) = 1.06-1.39, P = 0.005), population-based studies (heterozygous model: OR = 1.17, 95% CI = 1.02-1.34, P = 0.027), and among studies without the HWE (recessive model: OR = 1.42, 95% CI = 1.03-1.94, P = 0.030). When excluding three studies deviated from HWE, the significant results were also observed for heterozygous model in overall population (OR = 1.16, 95% CI = 1.02-1.31, P = 0.020). No publication bias was found in the present study. In conclusion, this meta-analysis suggests that MDM2 SNP309 polymorphism was associated with CRC susceptibility, especially among Asians. Further research is needed to assess possible gene-gene or gene-environment-lifestyle interactions on CRC.