title: CYP1A1 and GSTM1 genetic polymorphisms and lung cancer risk in Caucasian non-smokers: a pooled analysis.
abstract: Polymorphisms for genes encoding the metabolic enzymes cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) might contribute to the variability in individual susceptibility to lung cancer. The role of CYP1A1 and GSTM1 in lung carcinogenesis might be more important at low levels of exposure to carcinogens. Non-smokers represent a population at low exposure, however, they are often overlooked because of the small number of cases. We therefore conducted a pooled analysis of 14 case-control studies on lung cancer in Caucasian non-smokers with comparable information on genetic polymorphisms included in the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens. We pooled the raw data from a total of 302 cases and 1631 controls with random effects models. We also evaluated the possibility of inclusion bias and conducted influence analyses. The odds ratio (OR) of lung cancer for the variant CYP1A1 Ile(462)Val polymorphism (Ile/Val, Val/Val) was 2.99 [95% confidence interval (95%CI) 1.51-5.91]; this effect was stronger on lung adenocarcinoma (OR 4.85, 95%CI 2.03-11.6). After excluding outlying or imprecise studies, we did not observe a significant effect of the CYP1A1 MspI (T(3801)C) polymorphism or GSTM1 null genotype (OR 1.20, 95%CI 0.89-1.63). Furthermore, our analyses suggested a combined effect of the CYP1A1 Ile(462)Val polymorphism and GSTM1 null genotype. The OR for the combination of the CYP1A1 Ile(462)Val variant and GSTM1 null genotype was 4.67 (95%CI 2.00-10.9) compared with the concurrent presence of the CYP1A1 wild-type and GSTM1 non-null genotype. We did not observe a modification of the effect of the GSTM1 null genotype according to exposure to environmental tobacco smoke and urban/rural residence. Our study therefore suggests that the CYP1A1 Ile(462)Val variant allele might play a role in lung carcinogenesis among non-smokers, possibly in combination with the GSTM1 null genotype.
authors.affiliation: Unit of Environmental Cancer Epidemiology, International Agency for Research on Cancer, 150 Cours Albert-Thomas, F-69372 Lyon Cedex 08, France.
authors.forename: Rayjean J
authors.initials: RJ
authors.lastname: Hung
authors.forename: Paolo
authors.initials: P
authors.lastname: Boffetta
authors.forename: Jürgen
authors.initials: J
authors.lastname: Brockmöller
authors.forename: Dorota
authors.initials: D
authors.lastname: Butkiewicz
authors.forename: Ingolf
authors.initials: I
authors.lastname: Cascorbi
authors.forename: Margie L
authors.initials: ML
authors.lastname: Clapper
authors.forename: Seymour
authors.initials: S
authors.lastname: Garte
authors.forename: Aage
authors.initials: A
authors.lastname: Haugen
authors.forename: Ari
authors.initials: A
authors.lastname: Hirvonen
authors.forename: Sisko
authors.initials: S
authors.lastname: Anttila
authors.forename: Ivan
authors.initials: I
authors.lastname: Kalina
authors.forename: Loïc
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: London
authors.forename: Agneta
authors.initials: A
authors.lastname: Rannug
authors.forename: Marjorie
authors.initials: M
authors.lastname: Romkes
authors.forename: Jan
authors.initials: J
authors.lastname: Salagovic
authors.forename: Bernadette
authors.initials: B
authors.lastname: Schoket
authors.forename: Laura
authors.initials: L
authors.lastname: Gaspari
authors.forename: Emanuela
authors.initials: E
authors.lastname: Taioli
mesh_terms: D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D005787:Gene Frequency; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000453:epidemiology* / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking; D014481:United States / Q000453:epidemiology; D044465:White People
chemical_list: D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase