Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate whether sensitivity to the induction of micronuclei by acetaldehyde is associated with genetic polymorphisms of the aldehyde dehydrogenase-2 (ALDH2) gene, cytokinesis-block micronucleus (CBMN) assays were performed on peripheral lymphocytes from 47 healthy human subjects exposed to acetaldehyde in vitro. Facial flushing following alcohol intake was analyzed to determine if it was correlated with ALDH2 gene polymorphisms. The frequencies of the ALDH2 genotypes ALDH2(1)/ALDH2(1), ALDH2(1)/ALDH2(2), and ALDH2(2)/ALDH2(2) were 66.0, 27.7, and 6.4%, respectively, in the 47 subjects. Therefore, 34% of the studied subjects carried the mutant allele ALDH2(2), which is associated with the lack of enzyme activity. The frequency of micronuclei induced by acetaldehyde increased in a dose-dependent manner with the largest increase seen in subjects that were homozygous for the ALDH2(2) allele. A significant association was observed between the ALDH2 genotype and alcohol-induced facial flushing. Average alcohol consumption of the study subjects was also associated with the ALDH2 genotype. The frequency of heavy drinking was significantly higher among subjects with the ALDH2(1)/ALDH2(1) genotype than among subjects with the ALDH2(2) allele (ALDH2(1)/ALDH2(2) and ALDH2(2)/ALDH2(2) genotypes). Alcohol-induced facial flushing was also associated with an increased frequency of micronuclei in lymphocytes treated with acetaldehyde. The results suggest that the ALDH2 genotype is significantly associated with acetaldehyde-induced micronuclei and alcohol-induced facial flushing.
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PMID:Association of ALDH2 polymorphism with sensitivity to acetaldehyde-induced micronuclei and facial flushing after alcohol intake. 1584 Apr 30

Alcohol consumption is a risk factor for esophageal cancer. Acetaldehyde, a highly toxic intermediate produced from ethanol, is converted to acetic acid mainly by aldehyde dehydrogenase 2 (ALDH2) in the metabolic pathway of ethanol. Fifty percent of Japanese have inactive ALDH2 due to genetic polymorphism, which is considered to be a risk factor associated with esophageal cancer. In our previous study, we have demonstrated that ALDH2 is expressed in the esophagus with a considerable variation among individuals. In this study, we further investigated the expression of ALDH2 in esophagus and its relationship with risk factors of esophageal cancer. Tissue specimens resected from 51 patients with esophageal cancer were analyzed by immunohistochemistry using ALDH2-antibody. The immuno-staining of ALDH2 in the esophageal epithelium was compared with both the drinking habit and the occurrence of flushing that is closely associated with the ALDH2 deficiency. ALDH2 was not detectable in 8 (16%) among 51 specimens. All of the 8 patients were non- or light-drinkers but not heavy-drinkers. Among 18 patients showing the high level ALDH2 expression in the esophagus, 15 patients (83%) were heavy-drinkers. Although the relationship between the ALDH2 deficiency and drinking habit is not clear, the patients with ALDH2 deficiency tend to be non- or light drinkers while heavy-drinkers tend to have the active form of ALDH2. These results suggest that both inactive and active forms of ALDH2 are induced in the esophagus by heavy drinking and also support a hypothesis that ALDH2 deficiency might be a high-risk factor of esophageal cancer for the individuals having a heavy-drinking habit. To our knowledge, this is the first study demonstrating the induction of ALDH2 in the esophagus by ethanol consumption.
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PMID:Expression of aldehyde dehydrogenase 2 in the normal esophageal epithelium and alcohol consumption in patients with esophageal cancer. 1597 Apr 97

This review summarizes recent findings from human research regarding genetic influences in alcohol abuse and dependence. Genes explain about 50% of the vulnerabilities leading to heavy drinking and associated problems. Most genetic influences appear to impact at least four prominent intermediate characteristics (phenotypes) that interact with environmental events to produce the alcoholism risk: a flushing response to alcohol; a low level of response to alcohol; personality characteristics that include impulsivity, sensation seeking, and neuronal and behavioral disinhibition; and through psychiatric symptoms. Polymorphisms potentially related to each phenotype have been identified, and studies were conducted to evaluate their characteristics in the context of environmental and psychosocial forces. A search is underway to identify genes that contribute to these phenotypes; the ultimate goals of which are better prediction of how to best prevent heavy drinking and problems, identifying individuals who may respond best to existing treatments, and development of new therapeutic approaches based on the biological underpinnings of alcoholism.
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PMID:An overview of genetic influences in alcoholism. 1906 48

Both cigarette smoking and alcohol drinking are well-established risk factors for esophageal squamous cell carcinoma (ESCC), and the relationship of dose to cancer risk has already been described. Furthermore, the synergistic effect of these two factors has been reported. Our case-control study revealed the odds ratio of ESCC to be 50.1 for those who were both heavy smokers and heavy drinkers in comparison to people who neither drank nor smoked. In patients with ESCC, head and neck cancers as well as dysplastic lesions are frequently observed. Heavy smoking and heavy drinking are closely related to such multicentric carcinogenesis events in the upper aerodigestive tract (UADT), including the esophagus and head andneck region. Polymorphisms in acetaldehyde dehydrogenase 2 (ALDH2) are reported to be a key event in deciding individual susceptibility to UADT cancer. Patients with inactive ALDH2, in whom facial flushing is usually observed after the drinking of alcohol, are at high risk for ESCC as well as multiple UADT cancers. For the early detection of the disease, effective follow up using endoscopy with Lugol staining or narrow band imaging endoscopy is strongly recommended for high-risk populations, such as smokers, heavy drinkers, people with experience of flushing after the drinking of alcohol, and patients with UADT cancer.
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PMID:Alcohol drinking, cigarette smoking, and the development of squamous cell carcinoma of the esophagus: epidemiology, clinical findings, and prevention. 2022 84

The ethanol in alcoholic beverages and the acetaldehyde associated with alcohol consumption are Group 1 human carcinogens (WHO, International Agency for Research on Cancer). The combination of alcohol consumption, tobacco smoking, the inactive heterozygous aldehyde dehydrogenase-2 genotype (ALDH2*1/*2) and the less-active homozygous alcohol dehydrogenase-1B genotype (ADH1B*1/*1) increases the risk of squamous cell carcinoma (SCC) in the upper aerodigestive tract (UADT) in a multiplicative fashion in East Asians. In addition to being exposed to locally high levels of ethanol, the UADT is exposed to a very high concentration of acetaldehyde from a variety of sources, including that as an ingredient of alcoholic beverages per se and that found in tobacco smoke; acetaldehyde is also produced by salivary microorganisms and mucosal enzymes and is present as blood acetaldehyde. The inefficient degradation of acetaldehyde by weakly expressed ALDH2 in the UADT may be cri! tical to the local accumulation of acetaldehyde, especially in ALDH2*1/*2 carriers. ADH1B*1/*1 carriers tend to experience less intense alcohol flushing and are highly susceptible to heavy drinking and alcoholism. Heavy drinking by persons with the less-active ADH1B*1/*1 leads to longer exposure of the UADT to salivary ethanol and acetaldehyde. The ALDH2*1/*2 genotype is a very strong predictor of synchronous and metachronous multiple SCCs in the UADT. High red cell mean corpuscular volume (MCV), esophageal dysplasia, and melanosis in the UADT, all of which are frequently found in ALDH2*1/*2 drinkers, are useful for identifying high-risk individuals. We invented a simple flushing questionnaire that enables prediction of the ALDH2 phenotype. New health appraisal models that include ALDH2 genotype, the simple flushing questionnaire, or MCV are powerful tools for devising a new strategy for prevention and screening for UADT cancer in East Asians.
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PMID:Alcohol and aldehyde dehydrogenase polymorphisms and a new strategy for prevention and screening for cancer in the upper aerodigestive tract in East Asians. 2118 98