CYP1A1, GSTM1, and GSTT1 Polymorphisms, Smoking, and Lung Cancer Risk in a Pooled Analysis among Asian Populations

^{1 1}Department of Preventive Medicine, Seoul National University College of Medicine; ²Cancer Research Institute, Seoul National University, Seoul, Korea; ³Division of Population Science, Fox Chase Cancer Center, Philadelphia, Pennsylvania; ⁴Department of Physiological Chemistry, Karolinska Institutet, Stockholm, Sweden; ⁵Department of Global Health and Socio-Epidemiology, Kyoto University School of Public Health, Kyoto, Japan; ⁶Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; ⁷Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland; ⁸University of Hawaii-Cancer Research Center of Hawaii, Honolulu, Hawaii; ⁹National Health Research Institutes, Zhunan, Taiwan; ¹⁰Department of Biology and Center for Cancer Research, The Hong Kong University of Science and Technology, Kowloon, Hong Kong; ¹¹Department of Biochemistry, Faculty of Medicine, Cumhuriyet University, Sivas, Turkey; ¹²Cancer Epidemiology Unit, The University of Oxford, Oxford, United Kingdom; ¹³Cancer Control Unit, National Cancer Institute, Bangkok, Thailand; ¹⁴Department of Community, Occupational and Family Medicine, National University of Singapore, Singapore, Singapore; ¹⁵Department of Pathology, Hamamatsu University School of Medicine, Sizuoka, Japan; ¹⁶Department of Health Promotion and Preventive Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; ¹⁷Biology Division, National Cancer Center Research Institute, Tokyo, Japan; and ¹⁸University of Pittsburgh Cancer Institute and the University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania

^* To whom correspondence should be addressed. E-mail: dhkang{at}snu.ac.kr.

	Abstract

To evaluate the roles of CYP1A1 polymorphisms [Ile⁴⁶²Val and T⁶²³⁵C (MspI)] and deletion of GSTM1 and GSTT1 in lung cancer development in Asian populations, a pooled analysis was conducted on 13 existing studies included in Genetic Susceptibility to Environmental Carcinogenesis database. This pooled analysis included 1,971 cases and 2,130 controls. Lung cancer risk was estimated as odds ratios (OR) and 95% confidence intervals (95% CI) using unconditional logistic regression model adjusting for age, sex, and pack-year. The CYP1A1 ⁶²³⁵C variant was associated with squamous cell lung cancer (TC versus TT: OR, 1.42; 95% CI, 0.96-2.09; CC versus TT: OR, 1.97; 95% CI, 1.26-3.07; P_trend = 0.003). In haplotype analysis, ⁴⁶²Val-⁶²³⁵T and Ile-C haplotypes were associated with lung cancer risk with reference to the Ile-T haplotype (OR, 3.41; 95% CI, 1.78-6.53 and OR, 1.39; 95% CI, 1.12-1.71, respectively). The GSTM1-null genotype increased squamous cell lung cancer risk (OR, 1.36; 95% CI, 1.05-1.77). When the interaction was evaluated with smoking, increasing trend of lung cancer risk as pack-year increased was stronger among those with the CYP1A1 6235 TC/CC genotype compared with those with TT genotype (P_interaction = 0.001) and with the GSTM1-null genotype compared with the present type (P_interaction = 0.08, when no genotype effect with no exposure was assumed). These results suggest that genetic polymorphisms in CYP1A1 and GSTM1 are associated with lung cancer risk in Asian populations. However, further investigation is warranted considering the relatively small sample size when subgroup analyses were done and the lack of environmental exposure data other than smoking. (Cancer Epidemiol Biomarkers Prev 2008;17(5):1120–6)

Key Words: lung cancer, cytochrome P450, glutathione transferase, smoking, polymorphism, pooled analysis