CYP1A1 and GSTM1 genetic polymorphisms and lung cancer risk in Caucasian non-smokers: A pooled analysis

Rayjean J. Hung, Paolo Boffetta, Jürgen Brockmöller, Dorota Butkiewicz, Ingolf Cascorbi, Margie L. Clapper, Seymour Garte, Aage Haugen, Ari Hirvonen, Sisko Anttila, Ivan Kalina, Loïc Le Marchand, Stephanie J. London, Agneta Rannug, Marjorie Romkes, Jan Salagovic, B. Schoket, Laura Gaspari, Emanuela Taioli

Research output: Contribution to journalArticle

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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 Ile462 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 (T3801C) polymorphism or GSTM1 null genotype (OR 1.20, 95%CI 0.89-1.63). Furthermore, our analyses suggested a combined effect of the CYP1A1 Ile462Val polymorphism and GSTM1 null genotype. The OR for the combination of the CYP1A1 Ile462Val 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 Ile462Val variant allele might play a role in lung carcinogenesis among non-smokers, possibly in combination with the GSTM1 null genotype.

Original languageEnglish
Pages (from-to)875-882
Number of pages8
JournalCarcinogenesis
Volume24
Issue number5
DOIs
Publication statusPublished - May 1 2003

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Genetic Polymorphisms
Cytochrome P-450 Enzyme System
Lung Neoplasms
Genotype
Odds Ratio
Confidence Intervals
Carcinogenesis
Environmental Carcinogens
Lung
glutathione S-transferase M1
Environmental Exposure
Genetic Predisposition to Disease
Smoke
Carcinogens
Tobacco
Case-Control Studies
Alleles
Enzymes
Population
Genes

ASJC Scopus subject areas

  • Cancer Research

Cite this

Hung, R. J., Boffetta, P., Brockmöller, J., Butkiewicz, D., Cascorbi, I., Clapper, M. L., ... Taioli, E. (2003). CYP1A1 and GSTM1 genetic polymorphisms and lung cancer risk in Caucasian non-smokers: A pooled analysis. Carcinogenesis, 24(5), 875-882. https://doi.org/10.1093/carcin/bgg026

CYP1A1 and GSTM1 genetic polymorphisms and lung cancer risk in Caucasian non-smokers : A pooled analysis. / Hung, Rayjean J.; Boffetta, Paolo; Brockmöller, Jürgen; Butkiewicz, Dorota; Cascorbi, Ingolf; Clapper, Margie L.; Garte, Seymour; Haugen, Aage; Hirvonen, Ari; Anttila, Sisko; Kalina, Ivan; Le Marchand, Loïc; London, Stephanie J.; Rannug, Agneta; Romkes, Marjorie; Salagovic, Jan; Schoket, B.; Gaspari, Laura; Taioli, Emanuela.

In: Carcinogenesis, Vol. 24, No. 5, 01.05.2003, p. 875-882.

Research output: Contribution to journalArticle

Hung, RJ, Boffetta, P, Brockmöller, J, Butkiewicz, D, Cascorbi, I, Clapper, ML, Garte, S, Haugen, A, Hirvonen, A, Anttila, S, Kalina, I, Le Marchand, L, London, SJ, Rannug, A, Romkes, M, Salagovic, J, Schoket, B, Gaspari, L & Taioli, E 2003, 'CYP1A1 and GSTM1 genetic polymorphisms and lung cancer risk in Caucasian non-smokers: A pooled analysis', Carcinogenesis, vol. 24, no. 5, pp. 875-882. https://doi.org/10.1093/carcin/bgg026
Hung RJ, Boffetta P, Brockmöller J, Butkiewicz D, Cascorbi I, Clapper ML et al. CYP1A1 and GSTM1 genetic polymorphisms and lung cancer risk in Caucasian non-smokers: A pooled analysis. Carcinogenesis. 2003 May 1;24(5):875-882. https://doi.org/10.1093/carcin/bgg026
Hung, Rayjean J. ; Boffetta, Paolo ; Brockmöller, Jürgen ; Butkiewicz, Dorota ; Cascorbi, Ingolf ; Clapper, Margie L. ; Garte, Seymour ; Haugen, Aage ; Hirvonen, Ari ; Anttila, Sisko ; Kalina, Ivan ; Le Marchand, Loïc ; London, Stephanie J. ; Rannug, Agneta ; Romkes, Marjorie ; Salagovic, Jan ; Schoket, B. ; Gaspari, Laura ; Taioli, Emanuela. / CYP1A1 and GSTM1 genetic polymorphisms and lung cancer risk in Caucasian non-smokers : A pooled analysis. In: Carcinogenesis. 2003 ; Vol. 24, No. 5. pp. 875-882.
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AU - Hung, Rayjean J.

AU - Boffetta, Paolo

AU - Brockmöller, Jürgen

AU - Butkiewicz, Dorota

AU - Cascorbi, Ingolf

AU - Clapper, Margie L.

AU - Garte, Seymour

AU - Haugen, Aage

AU - Hirvonen, Ari

AU - Anttila, Sisko

AU - Kalina, Ivan

AU - Le Marchand, Loïc

AU - London, Stephanie J.

AU - Rannug, Agneta

AU - Romkes, Marjorie

AU - Salagovic, Jan

AU - Schoket, B.

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AU - Taioli, Emanuela

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