Polymorphisms of DNA repair gene XRCC1 in squamous cell carcinoma of the head and neck

Because reduced DNA repair capacity (phenotype) has been suggested as a ris k factor for squamous cell carcinoma of the head and neck (SCCHN), newly-id entified DNA repair gene polymorphisms (genotype) may also be implicated in risk. To test this hypothesis, we conducted a case-control study of 203 SC CHN patients and 424 control subjects (matched for age, sex and ethnicity) to investigate the role of two XRCC1 polymorphisms (XRCC1 26304 T and XRCC1 28152 A, respectively) in SCCHN. Multivariate logistic regression analysis was performed to calculate the adjusted odds ratio (OR) and 95% confidence interval (CI), A total of 180 cases (88.7%) and 363 controls (85.6%) lacke d the XRCC1 26304 T allele [adjusted OR = 1.34 (CI, 0.80-2.25)]. Lack of th is polymorphism was a significant risk factor specifically for cancers of t he oral cavity and pharynx [adjusted OR = 2.46 (CI, 1.22-4.97)]. Thirty-two cases (15.8%) and 46 controls (10.8%) were homozygous for the XRCC1 28152 A allele [adjusted OR = 1.59 (CI, 0.97-2.61) for all cases, and 1.41 (CI, 0 .80-2.48) for oral and pharyngeal cancer only]. Furthermore, when the two g enotypes were combined into a three-level model of risk, a polymorphism-pol ymorphism interaction of increasing risk (trend test, P = 0.049) was eviden t: OR = 1.0 for those with neither risk genotype (referent group), adjusted OR = 1.51 (CI, 0.87-2.61) for those with either risk genotype, and 2.02 (C I, 1.00-4.05) for those with both risk genotypes, For oral and pharyngeal c ancer, this trend was even more pronounced with the adjusted OR = 2.68 (CI, 1.28-5.61) for those with either risk genotype, and 3.22 (CI, 1.33-7.81) f or those with both risk genotypes, The findings support the hypothesis that a polymorphic XRCC1 DNA repair gene contributes to risk of developing SCCH N.