Acetylator Phenotype in Human Bladder Cancer

Miller, Marvin E.; Cosgriff, Janice M.

doi:10.1016/s0022-5347(17)50956-8

Cited by 36 publications

(14 citation statements)

References 4 publications

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“…Some studies of bladder cancer patients have suggested possible associations with the slow acetylator phenotype (Lower et al, 1979;Evans et al, 1983), including tumors related to occupational arylamine exposure (Cartwright et al, 1982), although one study found no relationship with acetylator status (Miller and Cosgriff, 1983). Abnormalities of tryptophan metabolism have long been suspected of playing a role in bladder cancer, and were observed in one high-risk family (Leklem and Brown, 1976), but not in others (Fraumeni and Thomas, 1967;McCullough et al, 1975) or in a population-based survey (Friedlander and Morrison, 1981).…”

Section: Discussionmentioning

confidence: 99%

Familial and environmental interactions in bladder cancer risk

Kantor

Hartge

Hoover

et al. 1985

Intl Journal of Cancer

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In a population-based study of 2,982 bladder cancer patients and 5,782 controls in 10 geographic areas of the United States which was designed to assess the role of environmental risk factors, information was also obtained on the history of urinary tract cancer in first-degree relatives. A family history of urinary tract cancer significantly elevated the risk of bladder cancer [relative risk (RR) = 1.45], with higher risks observed among patients under age 45. The risks of bladder cancer associated with positive family history were generally higher among persons with suspected environmental exposures, particularly heavy cigarette smoking (RR = 10.7 among those who smoked 3 or more packs per day). Further studies of bladder cancer should incorporate biochemical and genetic probes to assess mechanisms of familial susceptibility and interactions with environmental factors.

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Section: Discussionmentioning

confidence: 99%

Familial and environmental interactions in bladder cancer risk

Kantor

Hartge

Hoover

et al. 1985

Intl Journal of Cancer

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“…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.…”

Section: Nat2 Polymorphism and Urinary Bladder Cancer Riskmentioning

confidence: 99%

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

2006

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A role for the N-acetyltransferase 2 (NAT2) genetic polymorphism in cancer risk has been the subject of numerous studies. Although comprehensive reviews of the NAT2 acetylation polymorphism have been published elsewhere, the objective of this paper is to briefly highlight some important features of the NAT2 acetylation polymorphism that are not universally accepted to better understand the role of NAT2 polymorphism in carcinogenic risk assessment. NAT2 slow acetylator phenotype(s) infer a consistent and robust increase in urinary bladder cancer risk following exposures to aromatic amine carcinogens. However, identification of specific carcinogens is important as the effect of NAT2 polymorphism on urinary bladder cancer differs dramatically between monoarylamines and diarylamines. Misclassifications of carcinogen exposure and NAT2 genotype/phenotype confound evidence for a real biological effect. Functional understanding of the effects of NAT2 genetic polymorphisms on metabolism and genotoxicity, tissue-specific expression and the elucidation of the molecular mechanisms responsible are critical for the interpretation of previous and future human molecular epidemiology investigations into the role of NAT2 polymorphism on cancer risk. Although associations have been reported for various cancers, this paper focuses on urinary bladder cancer, a cancer in which a role for NAT2 polymorphism was first proposed and for which evidence is accumulating that the effect is biologically significant with important public health implications.

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“…In a number of studies of workers, slow acetylation has been reported as a risk factor for bladder cancer. [6][7][8][9][10][11][12] In several of these studies, workers were exposed to arylamine mixtures. 6,13 Other studies did not offer adequate detail of the exposure assessment or analytical methods employed.…”

mentioning

confidence: 99%

NAT2 slow acetylation and bladder cancer in workers exposed to benzidine

Carreón

Ruder

Schulte

et al. 2005

Intl Journal of Cancer

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This study expands a previous study of NAT2 polymorphisms and bladder cancer in male subjects occupationally exposed only to benzidine. The combined analysis of 68 cases and 107 controls from a cohort of production workers in China exposed to benzidine included 30 new cases and 67 controls not previously studied. NAT2 enzymatic activity phenotype was characterized by measuring urinary caffeine metabolite ratios. PCR-based methods identified genotypes for NAT2, NAT1 and GSTM1. NAT2 phenotype and genotype data were consistent. A protective association was observed for the slow NAT2 genotype (bladder cancer OR = 0.3; 95% CI = 0.1 = 1.0) after adjustment for cumulative benzidine exposure and lifetime smoking. Individuals carrying NAT1wt/*10 and NAT1*10/*10 showed higher relative risks of bladder cancer (OR = 2.8, 95% CI = 0.8-10.1 and OR = 2.2, 95% CI = 0.6-8.3, respectively). No association was found between GSTM1 null and bladder cancer. A metaanalysis risk estimate of case-control studies of NAT2 acetylation and bladder cancer in Asian populations without occupational arylamine exposures showed an increased risk for slow acetylators. The lower limit of the confidence interval (OR = 1.4; 95% CI = 1.0-2.0) approximated the upper confidence interval for the estimate obtained in our analysis. These results support the earlier finding of a protective association between slow acetylation and bladder cancer in benzidine-exposed workers, in contrast to its established link as a risk factor for bladder cancer in people exposed to 2-naphthylamine and 4-aminobiphenyl. Study findings suggest the existence of key differences in the metabolism of mono- and diarylamines.

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Acetylator Phenotype in Human Bladder Cancer

Cited by 36 publications

References 4 publications

Familial and environmental interactions in bladder cancer risk

Familial and environmental interactions in bladder cancer risk

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

NAT2 slow acetylation and bladder cancer in workers exposed to benzidine

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