Sequence variants of NAT1 and NAT2 and other xenometabolic genes and risk of lung and aerodigestive tract cancers in Central Europe

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
James D McKayPaul Brennan

Abstract

Tobacco smoke contains an extensive cocktail of highly carcinogenic chemicals. Individuals with a slower elimination rate of the chemicals in tobacco smoke may have increased exposure to their carcinogenic properties compared with those with a faster rate. Polymorphisms that alter the function of the genes involved in the activation or the detoxification of the chemical carcinogens in tobacco smoke can potentially influence an individual's risk of developing a tobacco-related cancer. To test this hypothesis, we have genotyped polymorphisms in 16 genes involved in metabolism of chemical carcinogens in a Central and Eastern European case-control study comprising 2,250 lung cases, 811 upper aerodigestive cancer (UADT) cases, and 2,704 controls. The N-acetyltransferase (NAT) genes were the most implicated in risk, with the NAT1*10 haplotype showing an inverse association in lung cancer, in both heterozygote carriers [odds ratio (OR), 0.81; 95% confidence interval (95% CI), 0.70-0.93] and homozygote carriers (OR, 0.70; 95% CI, 0.48-1.01), suggesting a genotype dose response (P < 0.001). In UADT cancer, a similar inverse association was noted in NAT1*10 although only in heterozygotes (OR, 0.78; 95%CI, 0.65-0.95). In NAT2, when consid...Continue Reading

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