Genetic polymorphisms of N-acetyltransferase 1 and 2 and risk of cigarette smoking-related bladder cancer

Abstract

Aromatic amines from cigarette smoking or occupational exposure, recognized risk factors for bladder cancer, are metabolized by N -acetyltransferases (NAT). This study examined the association of (NAT) 1 and 2 genotypes with the risk of smoking-related bladder cancer. A total of 74 pathologically confirmed bladder cancer patients and 184 controls were serially recruited from the National Taiwan University Hospital. History of cigarette smoking and other risk factors for bladder cancer was obtained through standardized questionnaire interview. Peripheral blood lymphocytes were collected from each subject and genotyped for NAT1 and NAT2 by DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism methods. Allele frequency distributions of NAT1 and NAT2 were similar between cases and controls. There was a significant dose–response relationship between the risk of bladder cancer and the quantity and duration of cigarette smoking. The biological gradients were significant among subjects carrying NAT1*10 allele or NAT2 slow acetylators, but not among NAT2 rapid acetylators without NAT1*10 allele. The results are consistent with the hypothesis that NAT1 and NAT2 might modulate the susceptibility to bladder cancer associated with cigarette smoking. © 1999 Cancer Research Campaign

N-acetyltransferase 2 genetic polymorphism: effects of carcinogen and haplotype on urinary bladder cancer risk

“…A previous review of 21 published case-control studies reported that experimental evidence was not sufficient to conclude a real increase in risk for urinary bladder cancer in slow NAT2 acetylators (Green et al, 2000). However, subsequent studies carried out in Europe (Vineis et al, 2001), Japan (Tsukino et al, 2004), the United States (Gu et al, 2005) and Spain (Garcia-Closas et al, 2005) each reported that NAT2 slow acetylators had a significantly increased risk of urinary bladder cancer that was stronger in smokers, (Woodhouse et al, 1982;Miller and Cosgriff, 1983;Hanssen et al, 1985;Ladero et al, 1985;Mommsen and Wolf, 1985;Karakaya et al, 1986;Kaisary et al, 1987;Horai et al, 1989;Dewan et al, 1995;Ishizu et al, 1995;Risch et al, 1995;Peluso et al, 1998;Su et al, 1998;Taylor et al, 1998;Hsieh et (Tsukino et al, 2004). Meta-analysis of these and all previous studies show that the overall association with slow NAT2 genotype in the published literature is robust (Figure 7) providing compelling evidence for a role of NAT2 acetylator genotype in urinary bladder cancer associated with aromatic amines in cigarette smoke.…”

N-acetyl transferase-2 and bladder cancer risk: A meta-analysis

“…Since then a large number of studies have appeared in the literature confirming or refuting an association between NAT2 status and bladder cancer risk [Woodhouse et al, 1982;Evans et al, 1983;Miller and Cosgriff, 1983;Hanssen et al, 1985;Ladero et al, 1985;Mommsen et al, 1985;Karakaya et al, 1986;Kaisary et al, 1987;Horai et al, 1989;Hanke and Krajewska, 1990;Hayes et al, 1993;Risch et al, 1995;Brockmoller et al, 1996;Okkels et al, 1997;Schnakenberg et al, 1998;Taylor et al, 1998;Filiadis et al, 1999;Hsieh et al, 1999]. In an attempt to clarify the effect of NAT2 status on bladder cancer risk, a meta-analysis of published studies has been undertaken.…”

N‐Acetyltransferase‐2, glutathione S‐transferase M1 and T1 genetic polymorphisms, cigarette smoking and hepatocellular carcinoma: A case‐control study

“…17 Regarding HCC, some studies have observed a significant association with NAT2 genetic polymorphisms, for both slow 18,19 and rapid 20 acetylator genotypes.…”