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 laryngeal cancer patients was genotyped for NAT1 and NAT2 and compared with 510 reference individuals, matched by age and gender. NAT1 genotypes (NAT13, 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 (NAT24/4 and NAT24/12A) amongst laryngeal cancer patients versus 19 (3.7%) such individuals in the control group (odds ratio 2.18, 95% confidence limits 1.13, 4.22; P = 0.018). Furthermore, an increasing NAT24/4 frequency in cases with strong cigarette consumption was observed, but also in non-smokers. Heterozygous genotypes of NAT24/slow were not overrepresented. These results correspond with earlier findings in lung cancer. Analysis of NAT1 and NAT2 combinations revealed a linkage disequilibrium between NAT110 and NAT24; NAT110 frequency was twofold higher in NAT2*4/4 carriers than in slow NAT2 coding genotypes. In conclusion, the distinct genotype NAT24/*4 proved to be a rare, but powerful host risk factor for larynx carcinoma. These data support the notion that an individual's specific NAT2 genotype may be decisive for the organ of his smoking-initiated cancer.