Frequency ofCYP2A6 gene deletion and its relation to risk of lung and esophageal cancer in the Chinese population

Tan, Wen; Chen, Gen Fu; Xing, De; Song, Chun Ying; Kadlubar, Fred F.; Lin, Dianliang

doi:10.1002/1097-0215(20010320)95:2<96::aid-ijc1017>3.0.co;2-2

Cited by 109 publications

(90 citation statements)

References 24 publications

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“…Table I shows the CYP2A6 genotype frequencies of our control group and the reported ethnic population. 5,9,13,15,20,21 Electrophoretic patterns of CYP2A6 *1/*1 and *1/*4 by polymerase chain reaction were the same pattern in our analysis method and did not discriminate CYP2A6 *1/*1 from *1/*4. There were significant interethnic differences in certain CYP2A6 genotype frequencies.…”

Section: Discussionmentioning

confidence: 61%

“…Decreasing cancer risk contributed by CYP2A6 gene deletion was in agreement with the hypothesis. Conversely, Tan et al 15 reported a significant association of CYP2A6 gene deletion with an increased risk of lung (OR ϭ 2.0, 95% CI 1.2-3.2) and esophageal cancer among non-smokers (OR ϭ 2.1, 95% CI 1.0 -4.5) in Chinese populations. Their result contradicted the hypothesis.…”

Section: Discussionmentioning

confidence: 96%

“…8,10 Several recent reports have investigated the role of CYP2A6 genetic polymorphisms in tobacco dependence and lung cancer risk, with conflicting results. [11][12][13][14][15] Less is known, however, about the role of CYP2A6 polymorphic enzymes in gastric cancer. There are few reports on CYP2E1 RsaI polymorphisms and gastric cancer.…”

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confidence: 99%

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Effects of cytochrome P450 (CYP) 2A6 gene deletion and CYP2E1 genotypes on gastric adenocarcinoma

Tsukino

Kuroda

Qiu

et al. 2002

Intl Journal of Cancer

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Cytochrome P450 (CYP) 2A6 and CYP2E1 are enzymes with a high ability to activate a nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), to its potent and ultimate carcinogens. The polymorphic CYP2A6 and CYP2E1 have been implicated in increased susceptibility to certain malignancies. In our study, 120 Japanese patients with gastric adenocarcinoma and 158 healthy controls were compared for frequencies of CYP2A6 and CYP2E1 genotypes. The frequency with which the subjects carried homozygotes of the CYP2A6 gene deletion allele, which causes lack of the enzyme activity, was significantly higher in the gastric cancer patients than in the healthy control subjects (OR ‫؍‬ 3.14, 95% confidence interval (95% CI) ‫؍‬ 1.05-9.41). Subdividing gastric adenocarcinoma according to tumor differentiation, patients with the well-differentiated type were 4. Although gastric cancer incidence has fallen markedly over the past 50 years in industrialized nations, it remains the second leading cause of cancer death in Japan. Epidemiological and experimental evidence have indicated that excess salt intake, which promotes cell replication, increases gastric cancer risk. 1,2 There is considerable evidence to support the view that carcinogenic N-nitrosamine derivatives are important factors in human cancer, including gastric cancer. The chemical mechanisms of carcinogenesis by these nitrosamines in humans are therefore of considerable interest. 3,4 Numerous studies have shown that several cytochrome P450 (CYP) enzymes, particularly cytochrome P4502A6 (CYP2A6) and cytochrome P4502E1 (CYP2E1), catalyze metabolic activation of nitrosamine derivatives, including N-nitroso-dialkyiamines and tobacco-smoke-related nitrosamine. [5][6][7][8] Genetic polymorphisms for CYP2A6 have been described and 2 variant alleles associated with reduced activity have been identified. Variant 1 (CYP2A6*2) and Variant 2 (CYP2A6*3) are the results of amino acid exchanged for wildtype (CYP2A6*1). Recently, Kitagawa et al. 9 revealed that a novel deletion genotype variant of the CYP2A6 gene was one of the major polymorphic genes in Japanese lacking CYP2A6 activity.In addition, CYP2E1 represents a major CYP isoform in the human liver and is also expressed in extrahepatic tissue. This enzyme can be induced by certain chemicals, such as ethanol and large interindividual variations have been observed, suggesting that the variation may be due to genetic polymorphism. It was reported that RsaI polymorphism, which is located in the 5Ј-flanking region of CYP2E1 gene, has been shown to be associated with the transcriptional regulation of gene expression, resulting in different expression levels of the CYP2E1 mRNA. 6 CYP2E1 participated in the metabolic activation of various N-nitrosamines, including a potent tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. 8,10 Several recent reports have investigated the role of CYP2A6 genetic polymorphisms in tobacco dependence and lung cancer risk, with conflicting results. [11][12][13][14][15] Less ...

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 96%

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Effects of cytochrome P450 (CYP) 2A6 gene deletion and CYP2E1 genotypes on gastric adenocarcinoma

Tsukino

Kuroda

Qiu

et al. 2002

Intl Journal of Cancer

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“…191,192 Inhibition of CYP2A6 activity in smokers increased clearance of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) glucuronide metabolite, suggesting a decreased metabolic activation of NNK and a shunting of NNK to detoxifying NNAL pathways. 193 The loss-of-function allele (CYP2A6*4) has been associated with a decreased risk of smoking-related cancers, 184,[194][195][196] whereas enhanced CYP2A6 activity, such as the duplication allele (CYP2A6*1X2), is predicted to increase risk.…”

Section: Other Likely Candidates Involved In Neurotransmitter Systemsmentioning

confidence: 99%

“…195,[197][198][199][200] One meta-analysis failed to find any association between CYP2A6 genotypes to smoking status or cigarette consumption, 201 although another found a modest effect of CYP2A6 on smoking cessation and cigarette consumption. 202 This may be owing to several factors, such as lack of statistical power, population stratification, different genotyping assays, the presence of many unidentified and uncharacterized CYP2A6 alleles (http://www.imm.ki.se/CYPalleles/cyp2a6.htm) among individuals designated as wild type and variations in definitions of smoking phenotypes/groups.…”

Section: Other Likely Candidates Involved In Neurotransmitter Systemsmentioning

confidence: 99%

Overview of the pharmacogenomics of cigarette smoking

Tyndale

2007

Pharmacogenomics J

102

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Cigarette smoking increases the risk of numerous health problems, including cancer, cardiovascular and pulmonary disorders, making smoking the leading cause of preventable death in the world. Nicotine is primarily responsible for the highly addictive properties of cigarettes. Although the majority of smokers express a desire to quit, few are successful in doing so. Twin and family studies have indicated substantial genetic contributions to smoking behaviors. One major research focus has been to elucidate the specific genes involved; this has been accomplished primarily through genome-wide linkage analyses and candidate gene association studies. Much attention has focused on genes involved in the neurotransmitter pathways for the brain reward system and genes altering nicotine metabolism. This paper reviews the current state of knowledge for genetic factors implicated in smoking behaviors, and examines how genetic variations may affect therapeutic outcomes for drugs used to assist smoking cessation.

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Polymorphism in cytochrome P4502A6 reduces the risk to head and neck cancer and modifies the treatment outcome

Yadav

Katiyar

Ruwali

et al. 2021

Environ and Mol Mutagen

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The present case-control study consisting of 1300 cases of head and neck squamous cell carcinoma (HNSCC) and the equal number of controls aimed to investigate the association of functionally important polymorphisms in cytochrome P4502A6 (CYP2A6*1B, CYP2A6*4C, CYP2A6*9-rs28399433) with HNSCC and the treatment response in cases receiving a combination of chemotherapy/radiotherapy (CT/RT). A significant decrease in risk to HNSCC was observed in the cases with deletion (CYP2A6*4B and CYP2A6*4C) or reduced activity genotypes (CYP2A6*9) of CYP2A6. This risk to HNSCC was further reduced significantly in tobacco users among the cases when compared to nontobacco users among the cases. The risk was also reduced to a slightly greater extent in alcohol users among the cases when compared to nonalcohol users among the cases. In contrast with decreased risk to HNSCC, almost half of the cases with variant genotypes of CYP2A6 (CYP2A6*1A/*4C+*1B/*4C+*4C/*4C and *9/*9) did not respond to the treatment. Likewise, the survival rate in cases receiving the treatment, after 55 months of follow-up was significantly lower in cases with deletion (6.3%) or reduced activity (11.9%) allele than in the cases with common alleles (41%). The present study has shown that CYP2A6 polymorphism significantly reduces the risk to HNSCC. Our data further suggested that CYP2A6 polymorphism may worsen the treatment outcome in the cases receiving CT/RT.

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Frequency ofCYP2A6 gene deletion and its relation to risk of lung and esophageal cancer in the Chinese population

Cited by 109 publications

References 24 publications

Effects of cytochrome P450 (CYP) 2A6 gene deletion and CYP2E1 genotypes on gastric adenocarcinoma

Effects of cytochrome P450 (CYP) 2A6 gene deletion and CYP2E1 genotypes on gastric adenocarcinoma

Overview of the pharmacogenomics of cigarette smoking

Polymorphism in cytochrome P4502A6 reduces the risk to head and neck cancer and modifies the treatment outcome

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