MGMT promoter-enhancer single nucleotide polymorphism rs16906252 is associated with MGMT promoter methylation in cancer

The methylation of the O(6)-methylguanine DNA methyltransferase (MGMT) promoter is frequently observed in several cancer types. The potential correlation between the C>T allele at SNP rs16906252 and methylation in MGMT are being actively investigated and remain largely elusive. We studied the allelic pattern of MGMT methylation through meta-analysis. All eligible studies were identified by searching PubMed, Web of Science, Embase, and Chinese National Knowledge Infrastructure Database. Pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated using fixedor random-effect model. Genotype and allelic frequency compared between cases and controls together with further subgroup analyses were carried out by cancer type. A total of 6 studies involving 1775 cancer cases were analyzed. Meta-analysis from this study indicated that the T allele of the rs16906252 SNP were strongly associated with increased risk for MGMT methylation in allelic model (OR = 9.70, 95% CI 4.12-22.86, Pheterogeneity = 0.021), heterozygote comparison OR = 11.28, 95% CI 4.46-28.52, Pheterogeneity = 0.024) and dominant model (OR = 6.61, 95% CI 3.23-13.54, Pheterogeneity = 0.003). Stratified analysis by cancer type indicated that the association became more prominent among glioblastoma, colorectal cancer and other cancer. Our study provides strong evidence that the T allele of a MGMT promoter-enhancer SNP is a key determinant for MGMT methylation in cancer. Clarifying this association could advance our knowledge of the influence of MGMT promoter-enhancer single nucleotide polymorphism rs16906252 on MGMT promoter methylation in cancer.