Metabolic gene polymorphisms and lung cancer risk in non-smokers. An update of the GSEC study.

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.

• Authors: 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, Agneta Rannug, Edyta Reszka, David Ryberg, Angela Risch, Marjorie Romkes, Alberto Ruano-Ravina, Bernadette Schoket, Monica Spinola, Haruhiko Sugimura, Xifeng Wu, Emanuela Taioli
• Journal: Mutation research (Mutat Res) Vol. 592 Issue 1-2 Pg. 45-57 (Dec 30 2005) ISSN: 0027-5107 [Print] Netherlands
• PMID: 16009381 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Cytochrome P-450 CYP1A1
• glutathione S-transferase T1
• Glutathione Transferase
• glutathione S-transferase M1

Topics

• Adenocarcinoma (epidemiology, genetics)
• Amino Acid Substitution
• Carcinoma, Squamous Cell (epidemiology, genetics)
• Cytochrome P-450 CYP1A1 (genetics)
• Environmental Exposure
• Genetic Predisposition to Disease
• Glutathione Transferase (genetics)
• Humans
• Lung Neoplasms (epidemiology, genetics)
• Polymorphism, Genetic
• Racial Groups
• Smoking Cessation
• United States