A PILOT-STUDY TESTING THE ASSOCIATION BETWEEN N-ACETYLTRANSFERASE-1 AND N-ACETYLTRANSFERASE-2 AND RISK OF ORAL SQUAMOUS-CELL CARCINOMA IN JAPANESE PEOPLE

Risk of oral cancer has been associated with exposure to tobacco smoke , alcohol and with genetic predisposition. The aromatic amines and the ir metabolites, a class of carcinogens present in tobacco smoke, under go metabolism (activation or detoxification) through an N- or O-acetyl ation pathway by the polymorphic enzymes, N-acetyltransferases (NAT)1 or NAT2, The genes that encode these enzymes, NAT1 and NAT2, have a va riety of high and low activity alleles and we analyzed these genetic p olymorphisms in 62 oral squamous cell carcinoma cases, and 122 healthy control subjects from Japan. NAT1 alleles tested were NAT13 (C1095A) , NAT14 (functional reference allele), NAT1*10 (T1088A,C1095A), NAT1* 11 (9 bp deletion), NAT114 (G560A), NAT1*15 (C559T) and NAT1*17 (C190 T). No low activity alleles (NAT114, NAT1*15 and NAT1*17) were observ ed in these Japanese subjects. We observed significantly increased ris k [odds ratio 3.72; 95% confidence interval (CI) 1.56-8.90; P < 0.01] associated with the NAT110 allele, an allele that contains a variant polyadenylation signal. Stratifying by smoking status we found odds ra tios 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 NAT110 alleles confer differential risk among smoker s and non-smokers. NAT2 rapid acetylation genotype was not a significa nt risk factor for oral cancer in this Japanese study population. This is the first study to test for oral cancer risk associated with polym orphism in the NAT1 and NAT2 genes, and these positive findings in our pilot study, while based on small numbers, suggest that the NAT110 a llele may be a genetic determinant of oral squamous cell carcinoma amo ng Japanese people.