Association of Arylamine N-acetyltransferases NAT1 and NAT2 Genotypes to Laryngeal Cancer Risk

Pharmacogenetics. 1999 Feb;9(1):103-11.

Abstract

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 (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 NAT2*4/*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 NAT2*4/*4 frequency in cases with strong cigarette consumption was observed, but also in non-smokers. Heterozygous genotypes of NAT2*4/slow were not overrepresented. These results correspond with earlier findings in lung cancer. Analysis of NAT1 and NAT2 combinations revealed a linkage disequilibrium between NAT1*10 and NAT2*4; NAT1*10 frequency was twofold higher in NAT2*4/*4 carriers than in slow NAT2 coding genotypes. In conclusion, the distinct genotype NAT2*4/*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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alcohol Drinking
  • Arylamine N-Acetyltransferase / genetics*
  • Base Sequence
  • DNA Primers
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Isoenzymes / genetics*
  • Laryngeal Neoplasms / genetics*
  • Male
  • Middle Aged
  • Risk Factors
  • Smoking

Substances

  • DNA Primers
  • Isoenzymes
  • Arylamine N-Acetyltransferase
  • N-acetyltransferase 1
  • NAT2 protein, human