title: Association between the risk for lung adenocarcinoma and a (-4) G-to-A polymorphism in the XPA gene.
abstract: Polymorphisms of genes coding for DNA repair can affect lung cancer risk. A common single nucleotide (-4) G-to-A polymorphism was identified previously in the 5' untranslated region of the XPA gene. In a case-control study in European Caucasians, the influence of this polymorphism on primary lung cancer risk overall and according to histologic subtypes was investigated. Four hundred sixty-three lung cancer cases (including 204 adenocarcinoma and 212 squamous cell carcinoma) and 460 tumor-free hospital controls were investigated using PCR amplification and melting point analysis of sequence-specific hybridization probes. Odds ratios (OR) were calculated by multiple logistic regression analysis adjusting for age, gender, smoking habits, and occupational exposure and showed a slightly enhanced risk for all lung cancer cases as well as for squamous cell carcinoma and adenocarcinoma cases. Gene-environment interactions were analyzed with respect to smoking and occupational exposure. A nearly 3-fold increased risk for adenocarcinoma associated with the XPA AA genotype was observed for occupationally exposed individuals (OR, 2.95; 95% confidence interval, 1.42-6.14) and for heavy smokers (OR, 2.52; 95% confidence interval, 1.17-5.42). No genotype-dependent increase in OR was found for nonexposed individuals or those smoking <20 pack-years. The significant effect of the XPA polymorphism in heavy smokers and occupationally exposed individuals suggests an important gene-environment interaction for the XPA gene. The underlying mechanisms as to why AA homozygotes are predisposed to lung adenocarcinoma and which specific carcinogens are involved remains to be determined.
authors.affiliation: Division of Toxicology and Cancer Risk Factors, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
authors.forename: Dorota
authors.initials: D
authors.lastname: Butkiewicz
authors.forename: Odilia
authors.initials: O
authors.lastname: Popanda
authors.forename: Angela
authors.initials: A
authors.lastname: Risch
authors.forename: Lutz
authors.initials: L
authors.lastname: Edler
authors.forename: Hendrik
authors.initials: H
authors.lastname: Dienemann
authors.forename: Volker
authors.initials: V
authors.lastname: Schulz
authors.forename: Klaus
authors.initials: K
authors.lastname: Kayser
authors.forename: Peter
authors.initials: P
authors.lastname: Drings
authors.forename: Helmut
authors.initials: H
authors.lastname: Bartsch
authors.forename: Peter
authors.initials: P
authors.lastname: Schmezer
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology* / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000209:etiology* / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000235:genetics*; D016022:Case-Control Studies; D004265:DNA Helicases; D004260:DNA Repair; D004268:DNA-Binding Proteins; D004777:Environment; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D051760:Xeroderma Pigmentosum Group A Protein
chemical_list: D004268:DNA-Binding Proteins; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein; D004265:DNA Helicases