Carcinogenesis, Vol 19, 1803-1807, Copyright © 1998 by Oxford University Press
T Katoh, S Kaneko, R Boissy, M Watson, K Ikemura and DA Bell
Risk of oral cancer has been associated with exposure to tobacco smoke,
alcohol and with genetic predisposition. The aromatic amines and their
metabolites, a class of carcinogens present in tobacco smoke, undergo
metabolism (activation or detoxification) through an N- or O- acetylation
pathway by the polymorphic enzymes, N-acetyltransferases (NAT)1 or NAT2.
The genes that encode these enzymes, NAT1 and NAT2, have a variety of high
and low activity alleles and we analyzed these genetic polymorphisms in 62
oral squamous cell carcinoma cases, and 122 healthy control subjects from
Japan. NAT1 alleles tested were NAT1*3 (C1095A), NAT1*4 (functional
reference allele), NAT1*10 (T1088A,C1095A), NAT1*11(9 bp deletion), NAT1*14
(G560A), NAT1*15 (C559T) and NAT1*17 (C190T). No low activity alleles
(NAT1*14, NAT1*15 and NAT1*17) were observed in these Japanese subjects. We
observed significantly increased risk [odds ratio 3.72; 95% confidence
interval (CI) 1.56-8.90; P < 0.01] associated with the NAT1*10 allele,
an allele that contains a variant polyadenylation signal. Stratifying by
smoking status we found odds ratios of 5.9 (95% CI 1.13-30.6; P < 0.05)
for non- smokers with the NAT1*10 allele and 3.1 (95% CI 1.09-9.07; P <
0.05) for smokers, but these risks were not significantly different from
each other. Thus, we did not observe that NAT1*10 alleles confer
differential risk among smokers and non-smokers. NAT2 rapid acetylation
genotype was not a significant risk factor for oral cancer in this Japanese
study population. This is the first study to test for oral cancer risk
associated with polymorphism in the NAT1 and NAT2 genes, and these positive
findings in our pilot study, while based on small numbers, suggest that the
NAT1*10 allele may be a genetic determinant of oral squamous cell carcinoma
among Japanese people.
ARTICLES
A pilot study testing the association between N-acetyltransferases 1 and 2 and risk of oral squamous cell carcinoma in Japanese people
National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
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