The role of O(6)-methylguanine-DNA methyltransferase polymorphisms in colorectal cancer susceptibility: a meta analysis.

Objective: O(6)-methylguanine DNA methyl-transferase gene (MGMT) is a central DNA repair mechanism with a significant role in removing DNA damage caused by alkylating agents and inhibiting human oncogenesis. Two single polymorphisms in the MGMT gene, Leu84Phe and Ile143Val, have been reported to affect DNA repair capability and enzymic activity, thereby leading to formation of different cancers. In this work, we quantitatively assess the associations between MGMT polymorphisms and risk of colorectal cancer (CRC), as previous studies has implicated inconsistencies in their results.

Methods: Analysis was performed on all usable data collected from the eligible studies that were searched in multiple bibliographical databases (PubMed, SCOPUS, and Embase).

Results: We obtained studies on Leu84Phe and Ile143Val, providing 6,154 and 7,371 samples, respectively. In the analysis on Leu84Phe, the SNP presented no global association with CRC at both the genotypic and the allelic level, but a trend towards an increased or decreased risk was shown in the models examined. Stratification by ethnicity revealed a significant increase in risk of CRC related to the Phe/Phe genotype in Caucasian samples (homozygote genetic model: OR=1.70, 95% CI=1.06-2.72; recessive genetic model: OR=1.80, 95% CI=1.12-2.87).

Conclusions: Based on the statistical data, our meta-analysis indicates that Leu84Phe polymorphism in the MGMT gene may predispose Caucasians to CRC.