Polymorphisms of Arylamine N-Acetyltransferase (NAT1 and NAT2) and Larynx Cancer Susceptibility

Varzim, Graça; Monteiro, Eurico; Silva, Regina; Pinheiro, Carlos da Justa; Lopes, Carlos

doi:10.1159/000058026

Cited by 18 publications

(19 citation statements)

References 16 publications

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“…Both NAT1 and NAT2 are considered major human detoxification systems to be able to acetylate carcinogenic arylamines found in the tobacco smoke. 15 Interestingly, NAT1, but not NAT2, is expressed in the laryngeal tissue. 22 According to Henning et al, 13 activation of arylamine carcinogens may be based on locally present NAT1, or they are transported from other sites to the larynx.…”

Section: Discussionmentioning

confidence: 99%

Genetic polymorphism of N‐acetyltransferase 2 in the susceptibility to laryngeal squamous cell carcinoma

et al. 2005

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Section: Discussionmentioning

confidence: 99%

Genetic polymorphism of N‐acetyltransferase 2 in the susceptibility to laryngeal squamous cell carcinoma

et al. 2005

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“…1,2 Polymorphisms at the NAT loci have been linked to susceptibility to a variety of different cancers, particularly in combination with exposure to carcinogenic arylamine or hydrazines, including cancer of the colon, 3 breast, 4 bladder 5 and larynx. 6 In humans there are two NAT isoforms with distinct but overlapping substrate specificities and tissue expression profiles, both of which exhibit interindividual variation in enzymic activity. 2 Human NAT2, expressed in liver and intestine, traditional sites for the expression of a drug metabolising enzyme, is responsible for the 'classical' polymorphic acetylation of the antitubercular drug isoniazid.…”

Section: Introductionmentioning

confidence: 99%

Generation and analysis of mice with a targeted disruption of the arylamine N-acetyltransferase type 2 gene

et al. 2003

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Arylamine N-acetyltransferases (NATs) are polymorphic xenobiotic metabolising enzymes, linked to cancer susceptibility in a variety of tissues. In humans and in mice there are multiple NAT isoforms. To identify whether the different isoforms represent inbuilt redundancy or whether they have unique roles, we have generated mice with a null allele of Nat2 by gene targeting. This mouse line conclusively demonstrates that the different isoforms have distinct functions with no compensatory expression in the Nat2 null animals of the other isoforms. In addition, we have used the transgenic line to show the pattern of Nat2 expression during development. Although Nat2 is not essential for embryonic development, it has a widespread tissue distribution from at least embryonic day 9.5. This mouse line now paves the way for the teratological role of Nat2 to be tested.

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“…Molecular epidemiologic studies suggest that genetic polymorphisms in NAT1 and NAT2 modify risk of developing certain cancers (245). For HNC, all 7 (100%) ORs (18,23,33,42,97,100,101) for the slow NAT2 genotype vs. the rapid genotype were >1, suggesting that the slow NAT2 genotype may be associated with an increased risk for HNC.EPHX1. The human microsomal epoxide hydrase (mEH), which is encoded by EPHX1, cleaves a range of alkene and arene oxides to form trans-dihydrodiols.…”

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Genetic polymorphisms and head and neck cancer risk (Review)

Hiyama¹,

Yoshihara²,

Tanaka³

et al. 2008

Int J Oncol

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Abstract. The aim of this report is to review and evaluate, in a comprehensive manner, the published data regarding the contribution of genetic polymorphisms to risk of head and neck cancer (HNC). All relevant studies available in MEDLINE and published before July 2007 were identified. Studies carried out in humans that compared HNC patients with at least 1 standard control group were considered for analysis. Two hundred and eighteen publications and 3 published metaanalyses were identified. Seventy-five (34%) studies were conducted in Asian, 72 (33%) in American, and 68 (31%) in European countries. The most widely studied gene was GSTM1 (58 studies), followed by GSTT1 (42 studies), GSTP1 (codon 105, 22 studies) and p53 (codon 72, 20 studies). GSTM1, GSTT1, GSTP1, XRCC1 codons 194 and 399, and CYP1A1 codon 462 were examined by meta-analyses, and significant relations were found between the GSTM1-null genotype and an increased risk for HNC. In addition, increased risk for HNC was associated consistently with the ALDH2*1/*2, p53 codon 72 Pro/Pro and EPHX1 codon 113 Tyr/His and His/His genotypes. Cohort studies that simultaneously consider multiple genetic and environmental factors possibly involved in carcinogenesis of the head and neck are needed to ascertain not only the relative contribution of these factors to tumor development but also the contributions of their putative interactions. IntroductionHead and neck cancers (HNCs), including cancers of the oral cavity, pharynx and larynx, represent the 6 most frequent cancers and the seventh leading cause of cancer-related death worldwide. There are approximately 540,000 new cases and 271,000 deaths annually worldwide for a mortality of approximately 50% (1). HNCs represent approximately 3% of all cancers in the United States whereas these cancers are much more prevalent in other areas of the world, such as India, Thailand and Brazil (1,2). Standard therapeutic approaches, which focus on surgery, irradiation and chemotherapy (alone or in combination), have been modified over the last 30 years; however, the overall survival of HNC patients has not improved substantially. For patients affected by early-stage cancers with a high disease-specific survival rate, secondary tumors represent the most common cause of death (3). Furthermore, patients with advanced cancers have a high risk of primary treatment failure and death.Development of HNC is a multifactorial process associated with a variety of risk factors. Major risk factors in developed countries include smoking tobacco and drinking alcohol, and chewing betel quid (4,5). For tobacco smoking, a dose-response trend has been reported. Relative risks of developing laryngeal and oropharyngeal cancers are 1.8 and 1.3, respectively, for persons who smoke ≤30 cigarettes per day and 7.7 and 2.9, respectively, for persons who smoke >30 cigarettes per day compared with non-smokers (6). Alcohol consumption is also linked to increased risk of HNCs. For persons who consume >4 drinks (=47.5 g of pure ethanol) per day, the relati...

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Polymorphisms of Arylamine N-Acetyltransferase (NAT1 and NAT2) and Larynx Cancer Susceptibility

Cited by 18 publications

References 16 publications

Genetic polymorphism of N‐acetyltransferase 2 in the susceptibility to laryngeal squamous cell carcinoma

Genetic polymorphism of N‐acetyltransferase 2 in the susceptibility to laryngeal squamous cell carcinoma

Generation and analysis of mice with a targeted disruption of the arylamine N-acetyltransferase type 2 gene

Genetic polymorphisms and head and neck cancer risk (Review)

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