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Hair dye use, genetic variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2), and risk of non-Hodgkin lymphoma.

ABSTRACT: BACKGROUND:Several previous studies have found non-Hodgkin lymphoma (NHL) risk to be associated with hair dye use, particularly use of permanent, dark colors and use before 1980, when hair dye formulations changed. METHODS:We examined NHL risk in relation to reported hair dye use among 1,321 cases and 1,057 controls from a US population-based multi-center study. DNA was extracted from blood or buccal cells to identify genetic variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2), which encode enzymes that metabolize aromatic amine compounds found in hair dyes. RESULTS:Among women, 509 cases and 413 controls reported hair dye use [odds ratio (OR) = 1.2; 95% confidence interval (95% CI) = 0.9, 1.6]. Risk estimates were higher for use before 1980 than for use in 1980 or later, particularly for use of permanent, intense tone (black, dark brown, dark blonde) products (<1980-OR = 1.6; 95% CI 0.9, 2.7; >or=1980-OR = 0.6; 95% CI 0.4, 1.1). Risk estimates were increased for women who used permanent, intense tone products before 1980 if they had the rapid/intermediate NAT2 phenotype (OR = 3.3; 95% CI 1.3, 8.6) or the NAT1 10 allele (OR = 2.5; 95% CI 0.9, 7.6), but not if they were slow NAT2 acetylators (OR = 1.5; 95% CI 0.6, 3.6) or had no copies of the NAT1 10 allele (OR = 1.5; 95% CI 0.7, 3.3). NHL risk was not increased among women who began hair dye use after 1980 or among men. CONCLUSION:Our results support previous research demonstrating elevated NHL risk among women who used dark color or intense tone permanent hair dyes before 1980. We present the first evidence suggesting that this risk may differ by genetic variation in NAT1 and NAT2.

SUBMITTER: Morton LM

PROVIDER: S-EPMC2085367 | biostudies-literature | 2007 Aug

REPOSITORIES: biostudies-literature

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Hair dye use, genetic variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2), and risk of non-Hodgkin lymphoma.

Morton Lindsay M LM Bernstein Leslie L Wang Sophia S SS Hein David W DW Rothman Nathaniel N Colt Joanne S JS Davis Scott S Cerhan James R JR Severson Richard K RK Welch Robert R Hartge Patricia P Zahm Shelia Hoar SH

Carcinogenesis 20070523 8

<h4>Background</h4>Several previous studies have found non-Hodgkin lymphoma (NHL) risk to be associated with hair dye use, particularly use of permanent, dark colors and use before 1980, when hair dye formulations changed.<h4>Methods</h4>We examined NHL risk in relation to reported hair dye use among 1,321 cases and 1,057 controls from a US population-based multi-center study. DNA was extracted from blood or buccal cells to identify genetic variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2), ...[more]

PMID: 17522066

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Project description:Acetyl Coenzyme A-dependent N-, O- and N,O-acetylation of aromatic amines and hydrazines by arylamine N-acetyltransferases is well characterised. Here, we describe experiments demonstrating that human arylamine N-acetyltransferase Type 1 and its murine homologue (Type 2) can also catalyse the direct hydrolysis of acetyl Coenzyme A in the presence of folate. This folate-dependent activity is exclusive to these two isoforms; no acetyl Coenzyme A hydrolysis was found when murine arylamine N-acetyltransferase Type 1 or recombinant bacterial arylamine N-acetyltransferases were incubated with folate. Proton nuclear magnetic resonance spectroscopy allowed chemical modifications occurring during the catalytic reaction to be analysed in real time, revealing that the disappearance of acetyl CH3 from acetyl Coenzyme A occurred concomitantly with the appearance of a CH3 peak corresponding to that of free acetate and suggesting that folate is not acetylated during the reaction. We propose that folate is a cofactor for this reaction and suggest it as an endogenous function of this widespread enzyme. Furthermore, in silico docking of folate within the active site of human arylamine N-acetyltransferase Type 1 suggests that folate may bind at the enzyme's active site, and facilitate acetyl Coenzyme A hydrolysis. The evidence presented in this paper adds to our growing understanding of the endogenous roles of human arylamine N-acetyltransferase Type 1 and its mouse homologue and expands the catalytic repertoire of these enzymes, demonstrating that they are by no means just xenobiotic metabolising enzymes but probably also play an important role in cellular metabolism. These data, together with the characterisation of a naphthoquinone inhibitor of folate-dependent acetyl Coenzyme A hydrolysis by human arylamine N-acetyltransferase Type 1/murine arylamine N-acetyltransferase Type 2, open up a range of future avenues of exploration, both for elucidating the developmental role of these enzymes and for improving chemotherapeutic approaches to pathological conditions including estrogen receptor-positive breast cancer.

Dataset Information

Hair dye use, genetic variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2), and risk of non-Hodgkin lymphoma.

Publications

Hair dye use, genetic variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2), and risk of non-Hodgkin lymphoma.

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