title: A systematic gene-gene and gene-environment interaction analysis of DNA repair genes XRCC1, XRCC2, XRCC3, XRCC4, and oral cancer risk.
abstract: Oral cancer is the sixth most common cancer worldwide with a high mortality rate. Biomarkers that anticipate susceptibility, prognosis, or response to treatments are much needed. Oral cancer is a polygenic disease involving complex interactions among genetic and environmental factors, which require multifaceted analyses. Here, we examined in a dataset of 103 oral cancer cases and 98 controls from Taiwan the association between oral cancer risk and the DNA repair genes X-ray repair cross-complementing group (XRCCs) 1-4, and the environmental factors of smoking, alcohol drinking, and betel quid (BQ) chewing. We employed logistic regression, multifactor dimensionality reduction (MDR), and hierarchical interaction graphs for analyzing gene-gene (G×G) and gene-environment (G×E) interactions. We identified a significantly elevated risk of the XRCC2 rs2040639 heterozygous variant among smokers [adjusted odds ratio (OR) 3.7, 95% confidence interval (CI)=1.1-12.1] and alcohol drinkers [adjusted OR=5.7, 95% CI=1.4-23.2]. The best two-factor based G×G interaction of oral cancer included the XRCC1 rs1799782 and XRCC2 rs2040639 [OR=3.13, 95% CI=1.66-6.13]. For the G×E interaction, the estimated OR of oral cancer for two (drinking-BQ chewing), three (XRCC1-XRCC2-BQ chewing), four (XRCC1-XRCC2-age-BQ chewing), and five factors (XRCC1-XRCC2-age-drinking-BQ chewing) were 32.9 [95% CI=14.1-76.9], 31.0 [95% CI=14.0-64.7], 49.8 [95% CI=21.0-117.7] and 82.9 [95% CI=31.0-221.5], respectively. Taken together, the genotypes of XRCC1 rs1799782 and XRCC2 rs2040639 DNA repair genes appear to be significantly associated with oral cancer. These were enhanced by exposure to certain environmental factors. The observations presented here warrant further research in larger study samples to examine their relevance for routine clinical care in oncology.
authors.affiliation: 1 Department of Electronic Engineering, National Kaohsiung University of Applied Sciences , Kaohsiung, Taiwan .
authors.forename: Cheng-Hong
authors.initials: CH
authors.lastname: Yang
authors.forename: Yu-Da
authors.initials: YD
authors.lastname: Lin
authors.forename: Ching-Yui
authors.initials: CY
authors.lastname: Yen
authors.forename: Li-Yeh
authors.initials: LY
authors.lastname: Chuang
authors.forename: Hsueh-Wei
authors.initials: HW
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking; D016022:Case-Control Studies; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009062:Mouth Neoplasms / Q000235:genetics*; D016017:Odds Ratio; D012306:Risk; D012907:Smoking; D013624:Taiwan; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human; C113187:XRCC2 protein, human; C101467:XRCC4 protein, human