VARIANTS OF N-ACETYLTRANSFERASE NAT1 AND A CASE-CONTROL STUDY OF COLORECTAL ADENOMAS

N-acetyltransferase NAT1, together with enzymes CYP1A2 and NAT2, helps convert heterocyclic amines to mutagens, Epidemiologic studies of the association of variants of these enzymes with colorectal cancer may p rovide indirect support for a heterocyclic amine mechanism. We used si ngle strand conformation polymorphism and heteroduplex analysis to scr een for mutations in the NAT1 coding region in a case-control study (n = 932) of colorectal adenomas, which are precursors to cancer, Thirte en different single-base mutations Were found: (CT)-T-97, (CT)-T-190, (TC)-C-402, G(445)A-G(459)A-T(640)G (a combination of three mutations) , (CT)-T-559, G(560)A, A(613)G, A(752)T, (TC)-C-777, G(781)A, and A(78 7)G. Function of novel mutations was tested by bacterial production of enzymes and measurement of K-m, V-max, and stability However, only 24 control individuals and 18 cases carried an inactivating NAT1 mutatio n. When combined with our data on the NAT2 acetylation polymorphism, w e saw no evidence for an association between N-acetyltransferases and prevalence of adenomas, Larger sample sizes are required for further e valuation. Pharmacogenetics 8:269-281 (C) 1998 Lippincott-Raven Publis hers.