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CYP1A1 I462V Genetic Polymorphism and Lung Cancer Risk in a Cohort of Men in Shanghai, China¹

Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709 [S. J. L.]; University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90033 [J-M. Y., G. A. C., R. K. R., M. C. Y.]; and Shanghai Cancer Institute, Shanghai, 2000 32 China [Y-T. G.]

Cytochrome P450 (CYP) CYP1A1 activates tobacco-related carcinogens. A point mutation at codon 462 in exon 7 of CYP1A1 results in a substitution of isoleucine by valine near the heme binding site. This mutation is rare in Caucasians but common in Japanese populations, in which association with increased risk of lung cancer has been reported. There are few data in other Asian populations. We investigated this I462V polymorphism using DNA from 214 incident cases of lung cancer and 669 controls in a prospective cohort study of 18,244 middle-aged and older men in Shanghai, China. The valine allele frequency was 0.138 among the control population. The I462V genotype was not appreciably associated with lung cancer risk overall. There was some suggestion that having at least one valine allele might be related to increased risk of lung cancer among smokers of <20 cigarettes/day (odds ratio, 1.72; 95% confidence interval, 0.82–3.62), particularly among those with homozygous deletion of GSTM1 (odds ratio, 2.80; 95% confidence interval, 1.07–7.33), which is involved in the detoxification of activated tobacco carcinogens. In this Chinese cohort, with CYP1A1 valine allele frequency intermediate between Japanese and Caucasian populations, the I462V polymorphism is not related to lung cancer overall, but it might play a role at lower levels of cigarette smoking among subjects with impaired carcinogen detoxification as assessed by the GSTM1-null genotype.

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