Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.1 (alcohol dehydrogenase)
 9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alcohol consumption interacts with tobacco use to increase the risk of head and neck squamous cell carcinoma (HNSCC). Alcohol is eliminated through oxidation by alcohol dehydrogenase (ADH). The ADH1C gene is polymorphic and the ADH1C*1 allele metabolizes ethanol to acetaldehyde at a higher rate than the variant ADH1C*2 allele. This polymorphism has been reported to alter the risk of HNSCC associated with alcohol use, although the literature differs in the estimates of both the magnitude and direction of this effect modification. We have investigated the association between the established risk factors for HNSCC and variant genotypes of ADH1C in a case-control study in the greater Boston area. ADH1C genotypes were determined from 521 cases and 599 population-based controls. The odds ratio (OR) for HNSCC associated with >26 drinks per week was 3.7 [95% confidence interval (95% CI), 2.4-5.7], whereas the OR for smoking >58 pack-years was 5.6 (95% CI, 3.8-8.4). The combination of heavy smoking and heavy drinking significantly interacted to produce an OR of 17.3 (95% CI, 7.8-38.3). In cases and controls, respectively, 16% and 14% were ADH1C*1-1, 46% and 46% were ADH1C*1-2 and 38% and 40% were ADH1C*2-2. There was a significant interaction of alcohol use and genotype (P = 0.05), with an estimated oral cancer risk in heavy drinkers of 7.1 (95% CI, 2.3-22.0) for homozygous variants compared with an OR of 2.3 (95% CI, 1.4-3.8) for ADH1C homozygous wild type or heterozygous individuals (controlling for smoking, age, race, and gender). These findings suggest that the ADH1C*2-2 genotype is associated with susceptibility to smoking and drinking-related HNSCC by modifying the biologically effective dose of alcohol.
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PMID:The ADH1C polymorphism modifies the risk of squamous cell carcinoma of the head and neck associated with alcohol and tobacco use. 1573 75

Alcohol is a well documented risk factor for upper digestive tract cancers. It has been shown that acetaldehyde, the first metabolite of ethanol is carcinogenic. The role of microbes in the production of acetaldehyde to the oral cavity has previously been described in several studies. In the present study, the aim was to investigate the capability of viridans group streptococci of normal oral flora to produce acetaldehyde in vitro during ethanol incubation. Furthermore, the aim was to measure the alcohol dehydrogenase (ADH) activity of the bacteria. Eight clinical strains and eight American Type Culture Collection (ATCC) strains of viridans group streptococci were selected for the study. Bacterial suspensions were incubated in two different ethanol concentrations, 11 mM and 1100 mM and the acetaldehyde was measured by gas chromatography. ADH-activity was measured by using a sensitive spectroscopy. The results show significant differences between the bacterial strains regarding acetaldehyde production capability and the detected ADH-activity. In particular, clinical strain of Streptococcus salivarius, both clinical and culture collection strains of Streptococcus intermedius and culture collection strain of Streptococcus mitis produced high amounts of acetaldehyde in 11 mM and 1100 mM ethanol incubation. All these four bacterial strains also showed significant ADH-enzyme activity. Twelve other strains were found to be low acetaldehyde producers. Consequently, our study shows that viridans group streptococci may play a role in metabolizing ethanol to carcinogenic acetaldehyde in the mouth. The observation supports the concept of a novel mechanism in the pathogenesis of oral cancer.
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PMID:Acetaldehyde production from ethanol by oral streptococci. 1685 55

We present a novel concept on carcinogenesis mediated by oral microbiota. Oral micro-organisms are capable of metabolizing alcohol to acetaldehyde. This finding casts light on the observed association between poor oral hygiene and oral cancer. Ethanol, as such, is not carcinogenic, but its first metabolite acetaldehyde is indisputably carcinogenic. Several gastro-intestinal microbial species possess the enzyme alcohol dehydrogenase (ADH), which is also the enzyme responsible for alcohol metabolism in the liver. In oral microbiota, we observed that species such as the ubiquitous viridans streptococci and Candida also possess ADH. Ethanol can be detected in the mouth hours after the consumption of alcoholic beverages. Patients with poor oral health status have shown higher salivary acetaldehyde concentrations than those with better oral health. It is thus understandable that ADH-containing micro-organisms in the mouth present a risk for carcinogenic acetaldehyde production, with subsequent potential for the development of oral cancer, particularly among heavy drinkers. In this article, we briefly review this area of investigation and conclude by highlighting some future possibilities for the control of carcinogenesis.
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PMID:Oral micro-organisms in the etiology of cancer. 1882 Oct 87

Oral cancer is the sixth most common cancer worldwide and a major health problem in some parts of the world. Epidemiological studies have shown that habitual alcohol consumption could be a risk factor in oral carcinogenesis, although the true involvement of alcohol is unknown. Via alcohol dehydrogenase (ADH) and cytochrome P450 oxidase (CYP) alcohol is metabolized to acetaldehyde, a highly toxic compound, which plays an important role in carcinogenesis. Subsequently, and during the metabolizing process, acetaldehyde becomes acetate by acetaldehyde dehydrogenase (ALDH). Therefore, acetaldehyde levels are determined mainly by the action of ADH, CYP and ALDH. Recently, several studies have found that certain polymorphisms of genes encoding these enzymes confer a higher or lower metabolic activity and therefore different risk for certain malignancies such as oral cancer. In this review, we analyze the polymorphisms of alcohol metabolising enzymes in relation susceptibility to an oral cancer.
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PMID:Oral cancer and polymorphism of ethanol metabolising genes. 1989 12

Alcohol consumption is a risk factor for oral cancer, possibly via its conversion to acetaldehyde, a known carcinogen. The oral commensal yeast Candida albicans may be one of the agents responsible for this conversion intra-orally. The alcohol dehydrogenase (Adh) family of enzymes are involved in acetaldehyde metabolism in yeast but, for C. albicans it is not known which family member is responsible for the conversion of ethanol to acetaldehyde. In this study we determined the expression of mRNAs from three C. albicans Adh genes (CaADH1, CaADH2 and CaCDH3) for cells grown in different culture media at different growth phases by Northern blot analysis and quantitative reverse transcription polymerase chain reaction. CaADH1 was constitutively expressed under all growth conditions but there was differential expression of CaADH2. CaADH3 expression was not detected. To investigate whether CaAdh1p or CaAdh2p can contribute to alcohol catabolism in C. albicans, each gene from the reference strain C. albicans SC5314 was expressed in Saccharomyces cerevisiae. Cell extracts from an CaAdh1p-expressing S. cerevisiae recombinant, but not an CaAdh2p-expressing recombinant, or an empty vector control strain, possessed ethanol-utilizing Adh activity above endogenous S. cerevisiae activity. Furthermore, expression of C. albicans Adh1p in a recombinant S. cerevisiae strain in which the endogenous ScADH2 gene (known to convert ethanol to acetaldehyde in this yeast) had been deleted, conferred an NAD-dependent ethanol-utilizing, and so acetaldehyde-producing, Adh activity. We conclude that CaAdh1p is the enzyme responsible for ethanol use under in vitro growth conditions, and may contribute to the intra-oral production of acetaldehyde.
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PMID:In vitro expression of Candida albicans alcohol dehydrogenase genes involved in acetaldehyde metabolism. 2497 85

Acetaldehyde is known to be carcinogenic and produced by oral bacteria. Thus, bacterial acetaldehyde production might contribute to oral cancer. Therefore, we examined bacterial acetaldehyde production from ethanol and glucose under various conditions mimicking the oral cavity and clarified the metabolic pathways responsible for bacterial acetaldehyde production. Streptococcus mitis, S. salivarius, S. mutans, Neisseria mucosa and N. sicca were used. The bacterial metabolism was conducted at pH 5.0-8.0 under aerobic and anaerobic conditions. The production of acetaldehyde and organic acids was measured with gas chromatography and HPLC, respectively. Bacterial enzymes were also assessed. All of the bacteria except for S. mutans exhibited their greatest acetaldehyde production from ethanol at neutral to alkaline pH under aerobic conditions. S. mutans demonstrated the greatest acetaldehyde from glucose under anaerobic conditions, although the level was much lower than that from ethanol. Alcohol dehydrogenase and NADH oxidase were detected in all of the bacteria. This study revealed that oral indigenous bacteria, Streptococcus and Neisseria can produce acetaldehyde, and that such acetaldehyde production is affected by environmental conditions. It was suggested that alcohol dehydrogenase and NADH oxidase are involved in ethanol-derived acetaldehyde production and that the branched-pathway from pyruvate is involved in glucose-derived acetaldehyde production.
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PMID:Metabolic property of acetaldehyde production from ethanol and glucose by oral Streptococcus and Neisseria. 3132 Jun 75

Oral cancer (OC) is among the top twenty occurring cancers in the world, with a mortality rate of 50%. A shift to a functionally inflammatory or a 'disease state' oral microbiome composition has been observed amongst patients with premalignant disorders and OC, with evidence suggesting alcohol could be exacerbating the inflammatory influence of the oral microorganisms. Alcohol dehydrogenase (ADH, EC 1.1.1.1) converts alcohol into a known carcinogenic metabolite, acetaldehyde and while ADH levels in oral mucosa are low, several oral commensal species possess ADH and could produce genotoxic levels of acetaldehyde. With a direct association between oral microbiome status, alcohol and poor oral health status combining to induce chronic inflammation with increased acetaldehyde levels - this leads to a tumour promoting environment. This new disease state increases the production of reactive oxygen species (ROS), while impairing anti-oxidant systems thus activating the redox signalling required for the promotion and survival of tumours. This review aims to highlight the evidence linking these processes in the progression of oral cancer.
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PMID:The interplay of the oral microbiome and alcohol consumption in oral squamous cell carcinomas. 3298 May 28