Polymorphic N-acetyltransferase (NAT2), an enzyme present in the colon, may affect incidence of colon cancer. Individuals with NAT2 fast acetylator genotypes may have higher colon cancer risks due to faster conversion of certain carcinogens to mutagens. We determined NAT2 genotypes in 447 subjects with distal colon adenomas and in 487 controls. No significant increase in adenoma prevalence among fast acetylators was observed. However, there was a suggestion of ethnic differences in NAT2 effects. For example, white fast acetylators potentially had slightly increased risks for adenomas (odds ratio, 1.29; 95% confidence interval, 0.90–1.84), whereas fast acetylation was potentially protective among blacks (odds ratio, 0.64; 95% confidence interval, 0.32–1.28). The apparent difference between blacks and whites may simply reflect random variation around an overall null effect, or it could represent a real difference. There was preliminary evidence for a possible interaction between NAT2 and the glutathione transferase M1 null genotype. Smokers' adenoma prevalence was 10-fold higher for fast acetylators with the null genotype compared to slow acetylators without the null genotype. Large, multiethnic populations and analysis of combinations of genes for carcinogen metabolism may be needed to further assess the role of NAT2 in colorectal tumorigenesis.


Supported in part by the Swiss League against Cancer (N. M. P-H.) and National Cancer Institute Grants 1R01CA63699 and 1R01CA51923 (R. W. H.). H. J. L. was supported by the UCLA Clinical Nutrition Research Unit, Cancer Research Foundation of America, March of Dimes (Basil O'Connor Awards 5-FY92-1216 and 5-FY93-0995), American Cancer Society Institutional Grant IN/IRG 131N to the Jonsson Comprehensive Cancer Center at UCLA, University of California Cancer Research Coordinating Committee, Wendy Will Case Cancer Fund, and Harbor Collegium at Harbor-UCLA Medical Center.

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