O6-methylguanine-DNA methyltransferase gene coding region polymorphisms and oral cancer risk

Background: O6-methylguanine-DNA methyltransferase (MGMT) is a specific DNA direct reversal repair protein which ameliorates mutagenic, carcinogenic and cytotoxic adducts from O6-methylguanine in DNA. The aim of this study was to investigate the potential association between six polymorphisms in the coding region of the MGMT gene and oral cancer risk in Taiwanese population. Methods: In this hospital-based case-control study, the MGMT genotypes were determined by using DNA sequencing in 176 patients with oral squamous cell carcinoma (OSCC), 77 patients with oral premalignant lesions and 110 normal individuals. Results: Although L53L and L84F polymorphisms were in complete linkage disequilibrium, no statistically significant association was found between the MGMT genotypes and haplotypes and oral cancer risk. We could also not detect any variations in the codon 65, 143, 160 and 178 within the coding region of the MGMT gene in both patients and controls. After stratification of OSCC patients by their mean age (54 years old), however, a higher overall survival rate with CT genotype than CC genotypes of the L53L polymorphisms was found in older patients (P = 0.031). A borderline significance (P = 0.074) between these genotypes and recurrence-free survivals has also been noted. The same results were also observed in L84F polymorphism. Conclusions: The present study did not find statistically significant association between six common MGMT polymorphisms and oral cancer risk, however, both MGMT L53L and L84F polymorphisms in old patients with CT genotype have higher overall survival rates than patients with CC genotype. Because of limited power of the present study, further study may be warranted in ethnically different populations to explore outcomes of these polymorphisms in the oral cancer risk.