HOMOZYGOUS RAPID ARYLAMINE N-ACETYLTRANSFERASE (NAT2) GENOTYPE AS A SUSCEPTIBILITY FACTOR FOR LUNG-CANCER

The polymorphic arylamine N-acetyltransferase (NAT2) is supposed to be a susceptibility factor for certain malignancies, A phenotyping study in 389 lung cancer patients revealed a similar distribution of rapid and slow acetylators by the caffeine test to that in 657 reference sub jects (odds ratio, 1.05; 95% confidence limits, 0.81, 1.36; not signif icant). A separate group of 155 lung cancer patients was studied by ge notyping NAT2 and was compared with a matched reference group of 310 u nrelated patients and with 278 healthy volunteers. The NAT2 genotype w as characterized by PCR-RFLP at nucleotide positions 191, 282, 341, 48 1, 590, 803, and 857. For evaluation of nucleotide 341, a 3'-mismatch primer was used. Homozygous wild-type genotypes NAT24/*4 were confirm ed by DNA sequencing, Genotypes for rapid acetylation amounted to 43.9 % among lung cancer and 41.6% among reference patients (odds ratio, 1. 10 95% confidence limits, 0.73, 1.65; not significant). Discrimination into homozygous and heterozygous carriers of allele NAT24 revealed a distinct overrepresentation of NAT24/*4 genotypes amid lung cancer p atients (odds ratio, 2.36; 95% confidence limits, 1.05, 5.32; P = 0.01 8). Logistic regression analysis considering sex, age, and smoking pro vided an odds ratio of 3.04 (95% confidence limits, 1.37, 6.75; P = 0. 003). Hence, carriers of the NAT24/*4 genotype, with its especially h igh acetylation capacity, are at significantly increased risk to lung cancer.