Interaction of Exo1 genotypes and smoking habit in oral cancer in Taiwan.

Exonuclease 1 (Exo1) is an important nuclease involved in the mismatch repair system that helps to maintain genomic stability, to modulate DNA recombination, and to mediate cell cycle arrest. Potential polymorphisms in Exo1 may alter cancer risks by influencing the repair activity of Exo1. Therefore, we hypothesized that single-nucleotide polymorphisms in Exo1 were associated with the risk of oral cancer. In this hospital-based study, the associations of Exo1 A-1419G (rs3754093), C-908G (rs10802996), A238G (rs1776177), C498T (rs1635517), K589E (rs1047840), G670E (rs1776148), C723R (rs1635498), L757P (rs9350) and C3114T (rs851797) polymorphisms with oral cancer risk in a central Taiwan population were investigated. In total, 680 patients with oral cancer and 680 age- and gender-matched healthy controls recruited from the China Medical University Hospital were genotyped. A significantly different distribution is found in the frequency of the Exo1 K589E genotype, but not the other genotypes, between the oral cancer and control groups. The A allele Exo1 K589E conferred a significant (P=6.18E-8) increased risk of oral cancer. Gene-environment interactions with smoking were significant for Exo1 K589E polymorphism (OR=2.509, 95% CI=1.914-3.287). Our results provide evidence that the A allele of the Exo1 K589E may be associated with the development of oral cancer.