Metabolic gene polymorphisms and lung cancer risk in non-smokers

An update of the GSEC study

Sara Raimondi, Paolo Boffetta, Sisko Anttila, Jürgen Bröckmoller, Dorota Butkiewicz, Ingolf Cascorbi, Margie L. Clapper, Tommaso A. Dragani, Seymour Garte, Andre Gsur, Gerald Haidinger, Ari Hirvonen, Magnus Ingelman-Sundberg, Ivan Kalina, Qing Lan, Vera Piera Leoni, Loïc Le Marchand, Stephanie J. London, Monica Neri, Andrew C. Povey & 11 others Agneta Rannug, Edyta Reszka, David Ryberg, Angela Risch, Marjorie Romkes, Alberto Ruano-Ravina, Bernadette Schoket, Monica Spinola, Haruhiko Sugimura, Xifeng Wu, Emanuela Taioli

Research output: Contribution to journalArticle

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Abstract

Background: Since genetic factors may play an important role in lung cancer development at low dose carcinogen exposure, non-smokers are a good model to study genetic susceptibility and its interaction with environmental factors. Materials and methods: We evaluated the role of the metabolic gene polymorphisms CYP1A1MspI, CYP1A1Ile462Val, GSTM1, and GSTT1 in non-smoker lung cancer patients from the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC). Non-smokers (defined as subjects who never smoked on a regular basis) were selected from the GSEC database. We pooled the raw data from 21 case-control studies for a total of 2764 Caucasians (555 cases and 2209 controls) and 383 Asians (113 cases and 270 controls). Tests of heterogeneity and of inclusion bias were performed. Results: A significant association between lung cancer and CYP1A1Ile462Val polymorphism was observed in Caucasians (adjusted OR = 2.04, 95% CI 1.17-3.54). GSTT1 deletion seems to be a risk factor for lung cancer in Caucasian non smokers only when the analysis was restricted to studies including healthy controls (adjusted OR = 1.66, 95% CI 1.12-2.46). A protective effect on lung cancer was observed with the combination of CYP1A1 wild type, GSTM1 null, and GSTT1 non-null genotypes. None of the analysed polymorphisms were associated with lung cancer in Asian non-smokers. Discussion: Our analysis confirms previous findings that CYP1A1Ile462Val polymorphism may play a role in lung carcinogenesis in Caucasian non-smokers.

Original languageEnglish
Pages (from-to)45-57
Number of pages13
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume592
Issue number1-2
DOIs
Publication statusPublished - Dec 30 2005

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Environmental Carcinogens
Genetic Predisposition to Disease
Lung Neoplasms
Genes
Cytochrome P-450 CYP1A1
Carcinogens
Case-Control Studies
Carcinogenesis
Genotype
Databases
Lung

Keywords

  • Epidemiology
  • Genetic susceptibility
  • Pooled analysis

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Molecular Biology

Cite this

Metabolic gene polymorphisms and lung cancer risk in non-smokers : An update of the GSEC study. / Raimondi, Sara; Boffetta, Paolo; Anttila, Sisko; Bröckmoller, Jürgen; Butkiewicz, Dorota; Cascorbi, Ingolf; Clapper, Margie L.; Dragani, Tommaso A.; Garte, Seymour; Gsur, Andre; Haidinger, Gerald; Hirvonen, Ari; Ingelman-Sundberg, Magnus; Kalina, Ivan; Lan, Qing; Leoni, Vera Piera; Marchand, Loïc Le; London, Stephanie J.; Neri, Monica; Povey, Andrew C.; Rannug, Agneta; Reszka, Edyta; Ryberg, David; Risch, Angela; Romkes, Marjorie; Ruano-Ravina, Alberto; Schoket, Bernadette; Spinola, Monica; Sugimura, Haruhiko; Wu, Xifeng; Taioli, Emanuela.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 592, No. 1-2, 30.12.2005, p. 45-57.

Research output: Contribution to journalArticle

Raimondi, S, Boffetta, P, Anttila, S, Bröckmoller, J, Butkiewicz, D, Cascorbi, I, Clapper, ML, Dragani, TA, Garte, S, Gsur, A, Haidinger, G, Hirvonen, A, Ingelman-Sundberg, M, Kalina, I, Lan, Q, Leoni, VP, Marchand, LL, London, SJ, Neri, M, Povey, AC, Rannug, A, Reszka, E, Ryberg, D, Risch, A, Romkes, M, Ruano-Ravina, A, Schoket, B, Spinola, M, Sugimura, H, Wu, X & Taioli, E 2005, 'Metabolic gene polymorphisms and lung cancer risk in non-smokers: An update of the GSEC study', Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, vol. 592, no. 1-2, pp. 45-57. https://doi.org/10.1016/j.mrfmmm.2005.06.002
Raimondi, Sara ; Boffetta, Paolo ; Anttila, Sisko ; Bröckmoller, Jürgen ; Butkiewicz, Dorota ; Cascorbi, Ingolf ; Clapper, Margie L. ; Dragani, Tommaso A. ; Garte, Seymour ; Gsur, Andre ; Haidinger, Gerald ; Hirvonen, Ari ; Ingelman-Sundberg, Magnus ; Kalina, Ivan ; Lan, Qing ; Leoni, Vera Piera ; Marchand, Loïc Le ; London, Stephanie J. ; Neri, Monica ; Povey, Andrew C. ; Rannug, Agneta ; Reszka, Edyta ; Ryberg, David ; Risch, Angela ; Romkes, Marjorie ; Ruano-Ravina, Alberto ; Schoket, Bernadette ; Spinola, Monica ; Sugimura, Haruhiko ; Wu, Xifeng ; Taioli, Emanuela. / Metabolic gene polymorphisms and lung cancer risk in non-smokers : An update of the GSEC study. In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. 2005 ; Vol. 592, No. 1-2. pp. 45-57.
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T2 - An update of the GSEC study

AU - Raimondi, Sara

AU - Boffetta, Paolo

AU - Anttila, Sisko

AU - Bröckmoller, Jürgen

AU - Butkiewicz, Dorota

AU - Cascorbi, Ingolf

AU - Clapper, Margie L.

AU - Dragani, Tommaso A.

AU - Garte, Seymour

AU - Gsur, Andre

AU - Haidinger, Gerald

AU - Hirvonen, Ari

AU - Ingelman-Sundberg, Magnus

AU - Kalina, Ivan

AU - Lan, Qing

AU - Leoni, Vera Piera

AU - Marchand, Loïc Le

AU - London, Stephanie J.

AU - Neri, Monica

AU - Povey, Andrew C.

AU - Rannug, Agneta

AU - Reszka, Edyta

AU - Ryberg, David

AU - Risch, Angela

AU - Romkes, Marjorie

AU - Ruano-Ravina, Alberto

AU - Schoket, Bernadette

AU - Spinola, Monica

AU - Sugimura, Haruhiko

AU - Wu, Xifeng

AU - Taioli, Emanuela

PY - 2005/12/30

Y1 - 2005/12/30

N2 - Background: Since genetic factors may play an important role in lung cancer development at low dose carcinogen exposure, non-smokers are a good model to study genetic susceptibility and its interaction with environmental factors. Materials and methods: We evaluated the role of the metabolic gene polymorphisms CYP1A1MspI, CYP1A1Ile462Val, GSTM1, and GSTT1 in non-smoker lung cancer patients from the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC). Non-smokers (defined as subjects who never smoked on a regular basis) were selected from the GSEC database. We pooled the raw data from 21 case-control studies for a total of 2764 Caucasians (555 cases and 2209 controls) and 383 Asians (113 cases and 270 controls). Tests of heterogeneity and of inclusion bias were performed. Results: A significant association between lung cancer and CYP1A1Ile462Val polymorphism was observed in Caucasians (adjusted OR = 2.04, 95% CI 1.17-3.54). GSTT1 deletion seems to be a risk factor for lung cancer in Caucasian non smokers only when the analysis was restricted to studies including healthy controls (adjusted OR = 1.66, 95% CI 1.12-2.46). A protective effect on lung cancer was observed with the combination of CYP1A1 wild type, GSTM1 null, and GSTT1 non-null genotypes. None of the analysed polymorphisms were associated with lung cancer in Asian non-smokers. Discussion: Our analysis confirms previous findings that CYP1A1Ile462Val polymorphism may play a role in lung carcinogenesis in Caucasian non-smokers.

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