TY - JOUR
T1 - Metabolic gene polymorphisms and lung cancer risk in non-smokers
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
N1 - Funding Information:
This work was funded in part by grants from European Commission (number 96/CAN/33919), Associazione and Fondazione Italiana Ricerca Cancro (airc and firc) and Associazione Marta Nurizzo, Italy, to TAD.
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.
AB - 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.
KW - Epidemiology
KW - Genetic susceptibility
KW - Pooled analysis
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U2 - 10.1016/j.mrfmmm.2005.06.002
DO - 10.1016/j.mrfmmm.2005.06.002
M3 - Article
C2 - 16009381
AN - SCOPUS:28244474053
SN - 0027-5107
VL - 592
SP - 45
EP - 57
JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
IS - 1-2
ER -