title: XPC polymorphisms and lung cancer risk.
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 smoking-related cancer. To test this hypothesis, we investigated the potential association of 7 XPC polymorphisms (-449G-->C, -371G-->A, -27G-->C, Val499Arg, PAT-/+, IVS11-5C-->A 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 frequency-matched for age and sex. XPC haplotypes were predicted using a Bayesian algorithm in the Phase program. The combined -27CG+CC genotype was associated with a significantly increased risk for overall lung cancer compared to the -27GG genotype (adjusted OR = 1.97, 95% CI 1.22-3.17, 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 -371AA genotype was associated with a significantly increased risk of squamous cell carcinoma compared to the combined -371GG and GA genotype (adjusted OR = 2.08, 95% CI 1.09-4.00, p = 0.03). The PAT-/+, IVS11-5C-->A 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 0.29-0.82, p = 0.006; adjusted OR = 0.60, 95% CI 0.36-1.00, p = 0.05; and adjusted OR = 0.58, 95% CI 0.35-0.97, p = 0.04, respectively). Consistent with genotyping analyses, haplotype 4 (1112222) containing the PAT+/IVS11-5A/939Gln alleles was associated with a significantly decreased risk of SM (adjusted OR = 0.56, 95% CI 0.37-0.85, p = 0.007 and Bonferroni-corrected p = 0.049), whereas haplotype 5 (1122111) containing the -27C allele was associated with a significantly increased risk of SM (adjusted OR = 2.88, 95% CI 1.41-5.87, p = 0.004 and Bonferroni-corrected p = 0.028). These results suggest that XPC polymorphisms/haplotypes may contribute to genetic susceptibility for lung cancer.
authors.affiliation: Cancer Research Institute, Kyungpook National University Hospital, Daegu, South Korea.
authors.forename: Ga Young
authors.initials: GY
authors.lastname: Lee
authors.forename: Jin-Sung
authors.initials: JS
authors.lastname: Jang
authors.forename: Sin Yeob
authors.initials: SY
authors.lastname: Lee
authors.forename: Hyo-Sung
authors.initials: HS
authors.lastname: Jeon
authors.forename: Kyung Mee
authors.initials: KM
authors.lastname: Kim
authors.forename: Jin Eun
authors.initials: JE
authors.lastname: Choi
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Park
authors.forename: Myung Hwa
authors.initials: MH
authors.lastname: Chae
authors.forename: Won Kee
authors.initials: WK
authors.lastname: Lee
authors.forename: Sin
authors.initials: S
authors.lastname: Kam
authors.forename: In-San
authors.initials: IS
authors.lastname: Kim
authors.forename: Jae-Tae
authors.initials: JT
authors.lastname: Lee
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Jung
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007723:Korea / Q000453:epidemiology; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D011503:Transglutaminases
chemical_list: D004268:DNA-Binding Proteins; C086984:XPC protein, human; D011503:Transglutaminases