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Cancer Epidemiology Biomarkers & Prevention 17, 1120-1126, May 1, 2008. Published Online First May 7, 2008;
doi: 10.1158/1055-9965.EPI-07-2786
© 2008 American Association for Cancer Research

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

Kyoung-Mu Lee1,7, Daehee Kang1,2, Margie L. Clapper3, Magnus Ingelman-Sundberg4, Masko Ono-Kihara5, Chikako Kiyohara6, Shen Min7, Qing Lan7, Loic Le Marchand8, Pinpin Lin9, Maria Li Lung10, Hatice Pinarbasi11, Paola Pisani12, Petcharin Srivatanakul13, Adeline Seow14, Haruhiko Sugimura15, Shinkan Tokudome16, Jun Yokota17 and Emanuela Taioli18

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

Requests for reprints: Daehee Kang, Department of Preventive Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul 110-799, Korea. Phone: 82-2-740-8326; Fax: 82-2-747-4830. E-mail: dhkang{at}snu.ac.kr

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; Ptrend = 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 (Pinteraction = 0.001) and with the GSTM1-null genotype compared with the present type (Pinteraction = 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)







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Copyright © 2008 by the American Association for Cancer Research.