N-acetyltransferase genetic polymorphism and susceptibility to bladder cancer

1997 Fiscal Year Final Research Report Summary

• Project/Area Number: 08671851
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Unuversity of Occupational and Environmental Health
• Principal Investigator: INATOMI Hisato University of Occupational and Environmental Health, School of Medicine, Research Associate, 医学部, 助手 (00193558)
• Project Period (FY): 1996 – 1997
• Keywords: Bladder canser / Urotherial canser / N-acetyltransferasel(NAT1) / N-acetyltransferase2(NAT2) / Genetic Polymorphism

Research Abstract

Various kinds of arylamines are involved in etiology of urethelial cancer (bladder cancer, renal pelvic and ureter cancer).
These compounds are acetylated by the two enzymes, N-acetyltransferase 1 (NAT1) and 2 (NAT2).
Epidemiological studies have shown that the phenotype oflow activity of NAT2 is associated with the increased risk for urothelial cancer.
Recently, a polymorphism was found at the polyadenylation signal site of the NAT1 gene and some alleles (the rapid NAT1 genotype) were reported to be associated with the increase camcer risk. We studied polymorphisms of the NAT1 or NAT2 genes among 115 urothelial cancer patients (UCG) (bladder canncer group (BCG) 85 cases, renal pelvic and ureter cancer group (PUCG) 30 cases, (66.9 (]SY.+-。[) 11.2) and 122 healthy controls (62.4 years (]SY.+-。[)16.6) in a Japanese population.
The PCR-RFLP technique was used to determine the NAT1 and NAT2 genotype.
The frequency of the rapid NAT1 genotype (BCG 74.1%, PUCG 73.3%, UCG (BCG+PUCG) 73.9%) was also higher among urothelial cancer cases versus control (62.3%) , however this increase did not reach a statistical significance. The frequency of the slow NAT2 genotype in patients with BCG (20.0%) , PUCG (16.7%) and UCG (19.1%) showed a statistically significant increase compared to that of the control group (5.7%). The odds ratio (OR) and 95% confidence interval (95%CI) were as follows : OR,4.11,95% CI,1.62-10.41 in BCG,OR,3.92,95% CI,0.96-11.20 in PUCG and OR,3.89,95% CI,1.59-9.50in UCG.Analysis of genetic combinations of NAT1/NAT2 alleles indicated that rapid NAT1/slow NAT2 genotype is associated with the high urothelial cancer risk. A case of normal NAT1/rapid NAT2 genotype was used as referent group to caliculate, the OR in rapid NAT1/slow NAT2 genotype was 7.56.