ARYLAMINE N-ACETYLTRANSFERASE-1 (NAT1) AND N-ACETYLTRANSFERASE-2 (NAT2) POLYMORPHISMS AN SUSCEPTIBILITY TO BLADDER-CANCER - THE INFLUENCE OF SMOKING

Aromatic amines are involved in the etiology of bladder cancer, These compounds are acetylated by N-acetyltransferase 1 (NAT1) and 2 (NAT2), and epidemiological studies have shown that the slow NAT2 acetylator phenotype is associated with increased risk of bladder cancer and may be associated with decreased risk of colorectal cancer, By using PCR-R FLP analyses to identify three known slow acetylator alleles (M1, M2, and M3) and the wild-type, or fast, allele, the NAT2 genotypes were de termined, No association between the NAT2 slow acetylator genotype and bladder cancer was found either by crude analyses [odds ratio (OR), 1 .32; 95% confidence interval (CI), 0.91-1.92) or by logistic regressio n analyses adjusted for age, gender, and smoking exposure (OR, 1.22; 9 5% CI, 0.92-1.62), A similar observation was made when the cases were divided into incident and surviving cases, Dividing the cases by patho logical classification (benign or malignant) did not alter this findin g, Likewise, analyses of the NAT1 and glutathione S-transferase mu 1 ( GSTM1) genotypes showed no associations between the NAT1 or GSTM1 geno types and bladder cancer risk. However, restricting the analysis to pe ople exposed to potential bladder carcinogens (i.e., smokers) among ca ses and controls, a small but significant association between the slow acetylator genotype and bladder cancer risk was revealed among all ca ses with malignant tumors (OR, 1.35; 95% CI, 1.02-1.80) and among inci dent cases with malignant tumors (OR, 1.50; 95% CI, 1.04-2.16), The al lele frequencies in the group consisting of smokers showed an overrepr esentation of the NAT2 M1 (NAT25) allele in the incident case group, The NAT1 and GSTM1 genotypes were not associated with increased risk o f bladder cancer among smokers, Analyses of genetic combinations of NA T1/NAT2 as potential risk factors for bladder cancer seem to indicate that the normal NAT1/fast NAT2 genotype may be a protective genotype c ompared with the other genotype combinations. Analyses of genetic comb inations of NAT2/GSTM1 did not reveal any combination of NAT2 and GSTM 1 genotypes associated with increased bladder cancer risk.