ORIGINAL ARTICLESGenetic variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2) and risk of non-Hodgkin lymphomaMorton, Lindsay M.a; Schenk, Maryjeanb; Hein, David W.c; Davis, Scottd; Zahm, Shelia Hoara; Cozen, Wendye; Cerhan, James R.f; Hartge, Patriciaa; Welch, Robertg; Chanock, Stephen J.g; Rothman, Nathaniela; Wang, Sophia S.a Author Information aDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, Maryland bKarmanos Cancer Institute and Department of Family Medicine, Wayne State University, Detroit, Michigan cDepartment of Pharmacology and Toxicology and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky dFred Hutchinson Cancer Research Center and the University of Washington, Seattle, Washington eUniversity of Southern California, Los Angeles, California fDepartment of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota and University of Iowa, Iowa City, Iowa gCore Genotyping Facility, Advanced Technology Center, National Cancer Institute, Gaithersburg, Maryland, USA Correspondence and requests for reprints to Lindsay M. Morton, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, 6120 Executive Boulevard, EPS/7073, MSC#7234, Rockville, MD 20852, USA Tel: +1 301 435 3972; fax: +1 301 402 0916; e-mail: [email protected] Sponsorship: This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, with Public Health Service (PHS) contracts N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010 and N02-PC-71105. Received 16 December 2005 Accepted 24 February 2006 Pharmacogenetics and Genomics: August 2006 - Volume 16 - Issue 8 - p 537-545 doi: 10.1097/01.fpc.0000215071.59836.29 Buy Metrics Abstract Animal studies suggest that lymphomagenesis can be induced by exposure to carcinogenic aromatic and heterocyclic amines found in diet, cigarette smoke and the environment, but human epidemiologic investigations of these exogenous exposures have yielded conflicting results. As part of our evaluation of the role of aromatic and heterocyclic amines, which are metabolized by N-acetyltransferase (NAT) enzymes, in the etiology of non-Hodgkin lymphoma (NHL), we examined NHL risk in relation to genetic variation in NAT1 and NAT2 and exposure to cigarette smoke and dietary heterocyclic amines and mutagens. We genotyped 10 common single nucleotide polymorphisms (SNPs) in NAT1 and NAT2 among 1136 cases and 922 controls from a population-based case–control study in four geographical areas of the USA. Relative risk of NHL for NAT1 and NAT2 genotypes, NAT2 acetylation phenotype, and exposure to cigarette smoke and dietary heterocyclic amines and mutagens was estimated using odds ratios (ORs) and 95% confidence intervals (CIs) derived from unconditional logistic regression models. We observed increased risk of NHL among individuals with the NAT1*10/*10 genotype compared with individuals with other NAT1 genotypes (OR=1.60, 95% CI=1.04–2.46, P=0.03). We also observed increased NHL risk in a dose-dependent model among NAT2 intermediate- and rapid-acetylators compared with slow-acetylators, although only the trend was statistically significant (intermediate: OR=1.18, 95% CI=0.97–1.44, P=0.1; rapid: OR=1.43, 95% CI=0.97–2.14, P=0.07; P for linear trend =0.03). Compared with non-smokers, NHL risk estimates for current cigarette smoking were increased only among NAT2 intermediate/rapid-acetylators (OR=2.44, 95% CI=1.15–5.20, P=0.02). Our data provide evidence that NAT1 and NAT2 genotypes are associated with NHL risk and support a contributory role for carcinogenic aromatic and/or heterocyclic amines in the multi-factorial etiology of NHL. © 2006 Lippincott Williams & Wilkins, Inc.