Relevance of N-acetyltransferase 1 and 2 (NAT1, NAT2) genetic polymorphisms in non-small cell lung cancer susceptibility

The highly polymorphic N-acetyltransferases (NAT1 and NAT2) are involved in both activation and inactivation reactions of numerous carcinogens, such a s tobacco derived aromatic amines. The potential effect of the NAT genotype s in individual susceptibility to lung cancer was examined in a hospital ba sed case-control study consisting of 392 Caucasian lung cancer patients [15 2 adenocarcinomas, 173 squamous cell carcinomas (SCC) and 67 other primary lung tumours] and 351 controls. In addition to the wild-type allele NAT1*4, seven variant NAT1 alleles (NAT1*3, *10, *11, *14, *15, *17 and *22) were analysed. A new method based on the LightCycler (Roche Diagnostics Inc.) te chnology was applied for the detection of the polymorphic NAT1 sites at nt 1088 and nt 1095. The NAT2 polymorphic sites at nt 481, 590, 803 and 857 we re detected by polymerase chain reaction-restriction fragment length polymo rphism or LightCycler. Multivariate logistic regression analyses were perfo rmed taking into account levels of smoking, age, gender and occupational ex posure. An increased risk for adenocarcinoma among the NAT1 putative fast a cetylators [odds ratio (OR) 1.92 (1.16-3.16)] was found but could not be de tected for SCC or the total case group. NAT2 genotypes alone appeared not t o modify individual lung cancer risk, however, individuals with combined NA T1 fast and NAT2 slow genotype had significantly elevated adenocarcinoma ri sk [OR 2.22 (1.03-4.81)] compared to persons with other genotype combinatio ns. These data clearly show the importance of separating different histolog ical lung tumour subtypes in studies on genetic susceptibility factors and implicate the NAT1*10 allele as a risk factor for adenocarcinoma, Pharmacog enetics 11:157-168 (C) 2001 Lippincott Williams & Wilkins.