Genetic variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2) and risk of non-Hodgkin lymphoma

Lindsay M. Morton, Maryjean Schenk, David W. Hein, Scott Davis, Shelia Hoar Zahm, Wendy Cozen, James R Cerhan, Patricia Hartge, Robert Welch, Stephen J. Chanock, Nathaniel Rothman, Sophia S. Wang

Research output: Contribution to journalArticle

45 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)537-545
Number of pages9
JournalPharmacogenetics and Genomics
Volume16
Issue number8
DOIs
StatePublished - Aug 2006

Fingerprint

Non-Hodgkin's Lymphoma
Amines
Odds Ratio
Confidence Intervals
Genotype
Smoke
Tobacco Products
Mutagens
Logistic Models
Acetyltransferases
N-acetyltransferase 1
Acetylation
Single Nucleotide Polymorphism
Case-Control Studies
Smoking
Diet
Phenotype
Enzymes
Population

Keywords

  • Genetic variation
  • N-acetyltransferase 1
  • N-acetyltransferase 2
  • Non-Hodgkin lymphoma
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Genetics
  • Pharmacology

Cite this

Morton, L. M., Schenk, M., Hein, D. W., Davis, S., Zahm, S. H., Cozen, W., ... Wang, S. S. (2006). Genetic variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2) and risk of non-Hodgkin lymphoma. Pharmacogenetics and Genomics, 16(8), 537-545. https://doi.org/10.1097/01.fpc.0000215071.59836.29

Genetic variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2) and risk of non-Hodgkin lymphoma. / Morton, Lindsay M.; Schenk, Maryjean; Hein, David W.; Davis, Scott; Zahm, Shelia Hoar; Cozen, Wendy; Cerhan, James R; Hartge, Patricia; Welch, Robert; Chanock, Stephen J.; Rothman, Nathaniel; Wang, Sophia S.

In: Pharmacogenetics and Genomics, Vol. 16, No. 8, 08.2006, p. 537-545.

Research output: Contribution to journalArticle

Morton, LM, Schenk, M, Hein, DW, Davis, S, Zahm, SH, Cozen, W, Cerhan, JR, Hartge, P, Welch, R, Chanock, SJ, Rothman, N & Wang, SS 2006, 'Genetic variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2) and risk of non-Hodgkin lymphoma', Pharmacogenetics and Genomics, vol. 16, no. 8, pp. 537-545. https://doi.org/10.1097/01.fpc.0000215071.59836.29
Morton, Lindsay M. ; Schenk, Maryjean ; Hein, David W. ; Davis, Scott ; Zahm, Shelia Hoar ; Cozen, Wendy ; Cerhan, James R ; Hartge, Patricia ; Welch, Robert ; Chanock, Stephen J. ; Rothman, Nathaniel ; Wang, Sophia S. / Genetic variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2) and risk of non-Hodgkin lymphoma. In: Pharmacogenetics and Genomics. 2006 ; Vol. 16, No. 8. pp. 537-545.
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