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-RFLP analyses to identify three known slow acetylator alleles (M1, M2, and M3) and the wild-type, or fast, allele, the NAT2 genotypes were determined. 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 regression analyses adjusted for age, gender, and smoking exposure (OR, 1.22; 95% CI, 0.92-1.62). A similar observation was made when the cases were divided into incident and surviving cases. Dividing the cases by pathological classification (benign or malignant) did not alter this finding. Likewise, analyses of the NAT1 and
glutathione S-transferase mu 1 (GSTM1) genotypes showed no associations between the NAT1 or GSTM1 genotypes and
bladder cancer risk. However, restricting the analysis to people exposed to potential bladder
carcinogens (i.e., smokers) among cases and controls, a small but significant association between the slow acetylator genotype and
bladder cancer risk was revealed among all cases with malignant
tumors (OR, 1.35; 95% CI, 1.02-1.80) and among incident cases with malignant
tumors (OR, 1.50; 95% CI, 1.04-2.16). The allele frequencies in the group consisting of smokers showed an overrepresentation of the NAT2 M1 (NAT2*5) allele in the incident case group. The NAT1 and GSTM1 genotypes were not associated with increased risk of
bladder cancer among smokers. Analyses of genetic combinations of NAT1/NAT2 as potential risk factors for
bladder cancer seem to indicate that the normal NAT1/fast NAT2 genotype may be a protective genotype compared with the other genotype combinations. Analyses of genetic combinations of NAT2/GSTM1 did not reveal any combination of NAT2 and GSTM1 genotypes associated with increased
bladder cancer risk.