N-acetyltransferase 2 gene polymorphism in patients with colorectal carcinoma

Tamer, Lülüfer; Ercan, Bahadır; Ateş, Nurcan Aras; Değirmenci, Ulaş; Ünlü, Ali; Ateş, Cengiz; Dirlik, Musa; Atik, Uğur

doi:10.1002/cbf.1191

Cited by 10 publications

(7 citation statements)

References 16 publications

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“…slow acetylation genotypes as the risk factor) [130,131], and finally an unexpected association with a rapid and a slow NAT2 variant allele in the same study [132] or increased frequency for a slow allele and decreased frequency for another slow allele among colorectal cancer patients [133], have been reported. The clinical significance of these findings is uncertain.…”

Section: Colon Cancermentioning

confidence: 98%

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: Colon Cancermentioning

confidence: 98%

Polymorphisms of Human N-Acetyltransferases and Cancer Risk

Agúndez

2008

CDM

123

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“…The data are controversial as regards about NAT2 fast phenotypes and the development different kinds of cancer. Some authors observed relation between phenotypes and/or genotypes NAT2 of fast acetylation and a higher risk of CRC development [123][124][125][126][127]. We may highlight the meta-analysis conducted by Ye & Parry (2002) that included 4,431 cases and 4,547 controls and observed that, for NAT2 fast phenotype individuals, there was a risk of 1.51 (95%CI = 1.07 -2.12) for CRC, while no relation was observed for NAT2 fast genotype individuals [128].…”

Section: Nat2 Fast Phenotypes In Cancer Susceptibilitymentioning

confidence: 99%

“…We may highlight the meta-analysis conducted by Ye & Parry (2002) that included 4,431 cases and 4,547 controls and observed that, for NAT2 fast phenotype individuals, there was a risk of 1.51 (95%CI = 1.07 -2.12) for CRC, while no relation was observed for NAT2 fast genotype individuals [128]. Some studies also suggest an increased CRC risk related to smoking and/or intake of red meat, associated to a higher frequency of NAT2 alleles of fast acetylation [106,107,125,126,[129][130][131][132][133][134][135][136]. When the risk association measure included smoking exposure and intake of alcohol, fast or intermediate NAT2 acetylator individuals (separately analyzed or in combination with other polymorphic genes), are more prevailing among patients with head and neck cancer [137][138][139][140][141].…”

Section: Nat2 Fast Phenotypes In Cancer Susceptibilitymentioning

confidence: 99%

N-acetyltransferase 2: Slow, intermediate or fast? A booming question of the molecular epidemiology in cancer research

Pietro¹,

Gadelha²,

Sousa³

et al. 2012

OJGen

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Throughout history, humanity has referred to reactions occurring with food, plants and, recently, medicines or drugs. The increase in pulmonary tuberculosis cases and the availability of treatment showed that genetic human differences can interfere in the capacity to metabolize drugs. There are remarkable genetic polymorphisms of N-acetyltransferase 2 (NAT2) activity that have been associated with different levels of susceptibility to developing many kinds of cancers. This review considers the field as an open window for the application of molecular epidemiology tools that led to the development of pharmacogenomics. We cover historical data and the most recent knowledge about NAT2 genetic polymorphisms and its distribution in different populations, which is an important concept being incorporated in epidemiological studies of cancer risk. We present up to date information about these studies, including meta-analysis based on the NAT2 distribution in different types of cancer. A critical broad at advances in NAT2 research, high-lighting recent studies related to NAT2 alleles in cancer susceptibility. Although there are multifactorial aspects involved in cancer risk, the variability in NAT2 allelic frequency can be related to carcinogenesis through alterations in the metabolic rate after exposure to carcinogens.

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“…Heterocyclic amine (HCA) from consumption of meat and fish could increase the risk for rectal cancer in men, but did not appreciably affect the risk for rectal cancer in women or for colon cancer in either sex (Le March et al , 2002; Chan et al 2005) reported an association between high intake of red meat and incidence of colorectal cancer risk, particularly among women with rapid acetylator NAT2 genotypes. Another study done in the southern region of Turkey suggested that the exposure to carcinogens through a high-protein diet might increase the risk of colorectal carcinoma only in genetically-susceptible individuals, with smoking status not differing between the control and patient group (Tamer et al , 2006). …”

Section: Discussionmentioning

confidence: 99%

Polymorphisms of arylamine N-acetyltransferase2 and risk of lung and colorectal cancer

et al. 2012

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The arylamine N-acetyltransferase 2 (NAT2) enzymes detoxify a wide range of naturally occurring xenobiotics including carcinogens and drugs. Point mutations in the NAT2 gene result in the variant alleles M1 (NAT2 *5A), M2 (NAT2*6A), M3 (NAT2*7) and M4 (NAT2 *14A) from the wild-type WT (NAT2 *4) allele. The current study was aimed at screening genetic polymorphisms of NAT2 gene in 49 lung cancer patients, 54 colorectal cancer patients and 99 cancer-free controls, using PCR-RFLP. There were significant differences in allele frequencies between lung cancer patients and controls in the WT, M2 and M3 alleles (p < 0.05). However, only M2 and M3 allele frequencies were different between colorectal cancer patients and controls (p < 0.05). There was a marginal significant difference in the distribution of rapid and slow acetylator genotypes between lung cancer patients and controls (p = 0.06 and p = 0.05, respectively), but not between colorectal cancer patients and controls (p = 1.0 and p = 0.95, respectively). Risk of lung cancer development was found to be lower in slow acetylators [odds ratio (OR): 0.51, 95% confidence interval (95% CI): 0.25, 1.02, p-value = 0.07]. No effect was observed in case of colorectal cancer. Our results showed that NAT2 genotypes and phenotypes might be involved in lung cancer but not colorectal cancer susceptibility in Jordan.

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N-acetyltransferase 2 gene polymorphism in patients with colorectal carcinoma

Cited by 10 publications

References 16 publications

Polymorphisms of Human N-Acetyltransferases and Cancer Risk

Polymorphisms of Human N-Acetyltransferases and Cancer Risk

N-acetyltransferase 2: Slow, intermediate or fast? A booming question of the molecular epidemiology in cancer research

Polymorphisms of arylamine N-acetyltransferase2 and risk of lung and colorectal cancer

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