Association between the risk for lung adenocarcinoma and a (-4) G-to-A polymorphism in the XPA gene.
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.
Butkiewicz
Dorota
D
Division of Toxicology and Cancer Risk Factors, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Popanda
Odilia
O
Risch
Angela
A
Edler
Lutz
L
Dienemann
Hendrik
H
Schulz
Volker
V
Kayser
Klaus
K
Drings
Peter
P
Bartsch
Helmut
H
Schmezer
Peter
P
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
D004268:DNA-Binding Proteins; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein; D004265:DNA Helicases