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

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• 作者：Sara Raimondi ; Paolo Boffetta ; Sisko Anttila ; Jü ; rgen Brö ; ckmoller ; Dorota Butkiewicz ; Ingolf Cascorbi ; Margie L. Clapper ; Tommaso A. Dragani ; Seymour Garte ; Andre Gsur et al.
• 刊名：Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis
• 出版年：2005
• 出版时间：30 December 2005
• 年：2005
• 卷：592
• 期：1-2
• 页码：45-57
• 全文大小：209 K

文摘

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.