Influence of CYP1A1, GSTM1, GSTT1, and NQO1 genotypes and cumulative smoking dose on lung cancer risk in a Swedish population.
The major identified risk factor for lung cancer is tobacco smoking. We identified previously the possible modifying influence of CYP1A1 and GSTM1 polymorphisms on lung cancer risk in a Swedish population. The present study, extended by several study subjects and with analyses for polymorphisms in GSTT1 and NQO1, includes 524 lung cancer cases and 530 control subjects. No evidence for an influence of genetic polymorphisms in CYP1A1, GSTM1, GSTT1, and NQO1 on lung cancer risk overall was found. In smokers, there was, however, a suggestion that the variant CYP1A1 and NQO1 genotypes may confer an increased risk for squamous cell carcinoma. In ever smokers, the homozygously deleted GSTM1 (GSTM1*O/*O) genotype was significantly associated with increased risk of small cell carcinoma (adjusted odds ratio 2.72, 95% confidence interval 1.32-5.90). The risks noted for the variant CYP1A1 genotypes and the GSTM1*O/*O genotype seemed to be restricted to light smokers. The GSTT1*O/*O genotype also appeared to be a possible risk factor in light smokers, whereas, in heavy smokers, this genotype was associated with decreased risk for lung cancer overall (odds ratio 0.36, 95% confidence interval 0.13-0.99). Due to the multiple comparisons made, we cannot exclude the possibility that some of these associations may represent chance findings.
Alexandrie
Anna-Karin
AK
Work Environment Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Nyberg
Fredrik
F
Warholm
Margareta
M
Rannug
Agneta
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018288:Carcinoma, Small Cell / Q000453:epidemiology* / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics; D013548:Sweden / Q000453:epidemiology
D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; C413545:glutathione S-transferase T1