Association of XRCC4 Codon 247 Polymorphism with Oral Cancer Susceptibility in Taiwan

Abstract

Background: The DNA repair gene XRCC4, an important caretaker of overall genome stability, is thought to play a major role in the development of human carcinogenesis. However, the association of the polymorphic variants of XRCC4 with oral cancer susceptibility has never been reported. Materials and Methods: In this hospital-based case-control study, the association of XRCC4 codon 247 (rs3734091), G-1394T (rs6869366), intron 7 (rs28360317) and intron 7 (rs1805377) polymorphisms with oral cancer risk in a Central Taiwanese population was investigated. In total, 318 patients with oral cancer and 318 age- and gender-matched healthy controls recruited from the China Medical Hospital in Central Taiwan were genotyped. Results: A significantly different distribution was found in the frequency of the XRCC4 codon 247 genotype, but not the XRCC4 G-1394T or intron 7 genotypes, between the oral cancer and control groups. A/C heterozygosity at XRCC4 codon 247 conferred a significant (2.04-fold) increased risk of oral cancer. As for XRCC4 G-1394T and intron 7 polymorphisms, there was no difference in distribution between the oral cancer and control groups. Gene-environment interactions with smoking, but not with betel quid chewing or alcohol consumption, were significant for XRCC4 codon 247 polymorphism. The XRCC4 codon 247 A/C genotype in association with smoking conferred an increased risk of 3.44 (95% confidence interval = 1.24-9.60) for oral cancer. Conclusion: Our results provide the first evidence that the heterozygous A allele of the XRCC4 codon 247 may be associated with the development of oral cancer and may be a novel useful marker for primary prevention and anticancer intervention.