Abstract
Polymorphisms in DNA repair genes may be associated with differences in the capacity to repair DNA damage and thereby influence an individual's susceptibility to smokingโrelated cancer. To test this hypothesis, we investigated the potential association of 7 XPC polymorphisms (โ449GโC, โ371GโA, โ27GโC, Val499Arg, PATโ/+, IVS11โ5CโA and Lys939Gln) and their haplotypes with lung cancer risk in a Korean population. XPC genotypes were determined in 432 lung cancer patients and 432 healthy controls frequencyโmatched for age and sex. XPC haplotypes were predicted using a Bayesian algorithm in the Phase program. The combined โ27CG+CC genotype was associated with a significantly increased risk for overall lung cancer compared to the โ27GG genotype (adjusted OR = 1.97, 95% CI 1.22โ3.17, p = 0.005). The other 6 polymorphisms were not significantly associated with overall risk of lung cancer. When lung cancer cases were categorized by tumor histology, the โ371AA genotype was associated with a significantly increased risk of squamous cell carcinoma compared to the combined โ371GG and GA genotype (adjusted OR = 2.08, 95% CI 1.09โ4.00, p = 0.03). The PATโ/+, IVS11โ5CโA and Lys939Gln polymorphisms were associated with a significantly decreased risk of small cell carcinoma (SM) under a dominant model for the polymorphic allele (adjusted OR = 0.49, 95% CI 0.29โ0.82, p = 0.006; adjusted OR = 0.60, 95% CI 0.36โ1.00, p = 0.05; and adjusted OR = 0.58, 95% CI 0.35โ0.97, p = 0.04, respectively). Consistent with genotyping analyses, haplotype 4 (1112222) containing the PAT+/IVS11โ5A/939Gln alleles was associated with a significantly decreased risk of SM (adjusted OR = 0.56, 95% CI 0.37โ0.85, p = 0.007 and Bonferroniโcorrected p = 0.049), whereas haplotype 5 (1122111) containing the โ27C allele was associated with a significantly increased risk of SM (adjusted OR = 2.88, 95% CI 1.41โ5.87, p = 0.004 and Bonferroniโcorrected p = 0.028). These results suggest that XPC polymorphisms/haplotypes may contribute to genetic susceptibility for lung cancer. ยฉ 2005 WileyโLiss, Inc.