Polymorphic <i>N</i>-acetylation capacity in lung cancer

Philip, P. A.; Fitzgerald, DL; Cartwright, R. A.; Peake, Michael; Rogers, H. J.

doi:10.1093/carcin/9.3.491

Cited by 19 publications

(4 citation statements)

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“…Phenotyping studies have shown no conclusive relationship of the acetylation status with lung cancer risk; rather, they have shown a reduction of the acetylation capacity of lung cancer patients as compared to healthy subjects [67][68][69]. Such an effect may be attributable either to paraneoplastic effects or to an over-representation of defect acetylation alleles in lung cancer patients.…”

Section: Lung Cancermentioning

confidence: 99%

Polymorphisms of Human N-Acetyltransferases and Cancer Risk

Agúndez

2008

CDM

123

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Human arylamine N-acetyltransferases (CoASAc; NAT, EC 2.3.1.5) NAT1 and NAT2 play a key role in the metabolism of drugs and environmental chemicals and in the metabolic activation and detoxification of procarcinogens. Phenotyping analyses have revealed an association between NAT enzyme activities and the risk of developing several forms of cancer. As genotyping procedures have become available for NAT1 and NAT2 gene variations, hundreds of association studies on NAT polymorphisms and cancer risk have been conducted. Here we review the findings obtained from these studies. Evidence for a putative association of NAT1 polymorphism and myeloma, lung and bladder cancer, as well as association of NAT2 polymorphisms with non-Hodgkin lymphoma, liver, colorectal and bladder cancer have been reported. In contrast, no consistent evidence for a relevant association of NAT polymorphisms with brain, head & neck, breast, gastric, pancreatic or prostate cancer have been described. Although preliminary data are available, further well-powered studies are required to fully elucidate the role of NAT1 in most human cancers, and that of NAT2 in astrocytoma, meningioma, esophageal, renal, cervical and testicular cancers, as well as in leukaemia and myeloma. This review discusses controversial findings on cancer risk and putative causes of heterogeneity in the proposed associations, and it identifies topics that require further investigation, particularly mechanisms underlying association of NAT polymorphisms and risk for subsets of cancer patients with specific exposures, putative epistatic contribution of polymorphism for other xenobiotic-metabolising enzymes such as glutathione S-transferases of Cytochrome P450 enzymes, and genetic plus environmental interaction.

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Section: Lung Cancermentioning

confidence: 99%

Polymorphisms of Human N-Acetyltransferases and Cancer Risk

Agúndez

2008

CDM

123

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“…Studies have been conflicting with regard to the association with lung cancer risk. Most studies report no overall increase in risk with either the slow or fast acetylators (Philip et al, 1988;Martinez et al, 1995;Bouchardy et al, 1998;Saarikoski et al, 2000), whereas a few have reported increased risk with either the slow (Oyama et al, 1997;Seow et al, 1999) or fast acetylator genotype. In the largest study of 1115 lung cancer patients and 1250 controls, no association was found between the NAT2 genotype and lung cancer risk (Zhou et al, 2002b).…”

Section: Carcinogen Metabolismmentioning

confidence: 99%

Genetic susceptibility to tobacco-related cancer

et al. 2004

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Although cigarette smoking is the dominant risk factor for several epithelial cancers, only a small fraction of individuals with tobacco exposure develop cancer. The underlying hypothesis is that genetic factors may render certain smokers more susceptible to cancer than others. Genetic alterations in critical regulatory pathways may predispose cells to carcinogenesis. These pathways include regulation of xenobiotic metabolism; control of genomic stability, including DNA repair mechanisms, cell-cycle checkpoints, apoptosis and telomere length; and control of microenvironmental factors, such as matrix metalloproteinases, inflammation and growth factors. In addition, epigenetic events, such as promoter hypermethylation and loss of imprinting, are also involved in carcinogenesis. In this review, we will summarize recent advances in genetic susceptibility to tobacco-related cancer. Emphasizing on risk assessment, we will describe how genetic variations in the above-mentioned genetic pathways modify the tobacco-related cancer risk. In addition, we will discuss how genetic variations may assist in predicting clinical outcome, such as the natural history of cancer and treatment response. The measurements of genetic susceptibility by both genotypic and phenotypic assays are covered in the text. Finally, we present a number of current concerns that need to be addressed as the exciting field of molecular cancer epidemiology advances rapidly.

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“…For instance, in the case of lung cancer there are numerous potential contributors, including polycyclic hydrocarbons, aryl and heterocyclic amines, and nitrosamines. Some convincing evidence has been presented for a role of Nacetyltransferase polymorphism in bladder and colon cancers [Philip et al, 1988;d'Errico et al, 1996]. Epidemiological evidence for a role of P450 1A2 (high level) in bladder cancer has been seen but only in combination with N-acetyltransferase [Lang et al, 1994].…”

Section: Significance Of Variabilitymentioning

confidence: 99%

Pharmacogenomics of cytochrome P450 and other enzymes involved in biotransformation of xenobiotics

Guengerich

2000

Drug Dev. Res.

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Polymorphic N-acetylation capacity in lung cancer

Cited by 19 publications

References 0 publications

Polymorphisms of Human N-Acetyltransferases and Cancer Risk

Polymorphisms of Human N-Acetyltransferases and Cancer Risk

Genetic susceptibility to tobacco-related cancer

Pharmacogenomics of cytochrome P450 and other enzymes involved in biotransformation of xenobiotics

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