Association of arylamine N-acetyltransferases NAT1 and NAT2 genotypes to laryngeal cancer risk

Genetically polymorphic xenobiotic metabolizing enzymes are supposed to be host factors for an individual's cancer susceptibility. A total of 255 lary ngeal cancer patients was genotyped for NAT1 and NAT2 and compared with 510 reference individuals, matched by age and gender. NAT1 genotypes (NAT1*3, *4, *10, and *11) were found equally distributed between cases and control individuals, However, there was a significant overrepresentation of 20 (7.8 %) homozygous NAT2 genotypes coding for rapid acetylation (NAT2*4/*4 and NA T2*4/*12 A) amongst laryngeal cancer patients versus 19 (3.7%) such individ uals in the control group (odds ratio 2.18, 95% confidence limits 1.13, 4.2 2; P = 0.018). Furthermore, an increasing NAT2*4/*4 frequency in cases with strong cigarette consumption was observed, but also in non-smokers, Hetero zygous genotypes of NAT2*4/slow were not overrepresented. These results cor respond with earlier findings in lung cancer, Analysis of NAT1 and NAT2 com binations revealed a linkage disequilibrium between NAT1*10 and NAT2*4; NAT 1*10 frequency was twofold higher in NAT2*4/*4 carriers than in slow NAT2 c oding genotypes. In conclusion, the distinct genotype NAT2*4/*4 proved to b e a rare, but powerful host risk factor for larynx carcinoma. These data su pport the notion that an individual's specific NAT2 genotype may be decisiv e for the organ of his smoking-initiated cancer. Pharmacogenetics 9:103-111 (C) 1999 Lippincott Williams & Wilkins.