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

Epidemiology has demonstrated that alcoholic beverages are causally related to oropharyngolaryngeal, esophageal, liver, colorectal, and female breast cancer. Among Japanese male alcoholics screened by endoscopy combined with esophageal iodine staining and immunofecal occult blood tests, 4.2% had esophageal squamous cell carcinoma (SCC); 1.2%, oropharyngolaryngeal SCC; 1.4%, stomach adenocarcinoma; 1.9%, colorectal adenocarcinoma. The inactive form of aldehyde dehydrogenase-2 (ALDH2), encoded by the gene ALDH2*1/2*2, which is prevalent in Asians, exposes them to higher levels of acetaldehyde after drinking and was a strong risk factor for these cancers among Japanese heavy drinkers. Inactive ALDH2 was also associated with synchronous and metachronous multiple esophageal cancers. These results suggest a general role of acetaldehyde, an established animal carcinogen, in carcinogenesis of the human alimentary tract. The oropharyngolarynx and esophagus lack ALDH2 activity, suggesting that after exposure to acetaldehyde derived from systemic, mucosal, salivary, or bacterial production or alcoholic beverages, these organs' inefficient degradation of acetaldehyde enhances the chances for local acetaldehyde-associated carcinogenesis. The normal alcohol dehydrogenase-2 (ADH2), encoded by ADH2*1/2*1, is another risk factor for oropharyngolaryngeal and esophageal cancer in Japanese alcoholics. For patients with both normal ADH2 and inactive ALDH2, the risks for oropharyngolaryngeal and esophageal cancer are enhanced in a multiplicative fashion. The responses to a simple questionnaire about both current and past facial flushing after drinking a glass of beer can indicate an individual's ALDH2 phenotype fairly well. Use of this questionnaire to obtain information on ALDH2-associated cancer susceptibility could contribute to the prevention of alcohol-related cancer in Asians.
 ...
PMID:[Alcohol and oropharyngolaryngeal and digestive tract cancer]. 1182 13

Aldehyde dehydrogenase-2 (ALDH2) is a key enzyme for the elimination of acetaldehyde, an established animal carcinogen generated by alcohol metabolism. In the presence of ALDH2*2, a mutant allele that is prevalent in East Asians, this enzyme is inactive, leading to excessive accumulation of acetaldehyde. Only among Japanese alcoholic patients has the positive association between this inactive form of ALDH2 and multiple-field cancerization in the upper aerodigestive tract been demonstrated. Whether this finding could be extended to multiple-cancer patients in general is of great interest, because the prevalence of esophageal cancer with other organ cancers has increased dramatically during recent decades in Japan. This study compared the ALDH2 genotypes of groups of male Japanese drinkers who had either esophageal squamous cell carcinomas (SCCs) with (n = 26) or without (n = 48) multiplicity or oropharyngolaryngeal SCCs with (n = 17) or without (n = 29) multiplicity. After adjustments for age and drinking and smoking habits, logistic regression analysis showed significantly increased risk for each multiplicity associated with either esophageal or oropharyngolaryngeal SCCs in the presence of the ALDH2*2 allele (odds ratio, 5.26; 95% confidence interval, 1.08-51.06 and odds ratio, 7.36; 95% confidence interval, 1.29-80.70, respectively). This study is the first to strongly link inactive ALDH2 with the multiple cancer susceptibility of male Japanese drinkers with either esophageal or oropharyngolaryngeal cancers. A simple questionnaire about both current and past facial flushing after drinking a glass of beer was highly sensitive (95.6%) in detecting inactive ALDH2 in these patients and may be useful for identifying high-risk patients.
 ...
PMID:Multiple cancers associated with esophageal and oropharyngolaryngeal squamous cell carcinoma and the aldehyde dehydrogenase-2 genotype in male Japanese drinkers. 1222 35

We investigated the effects of extracts from the dried flower of Pueraria thomsonii on blood ethanol and acetaldehyde levels in humans consuming alcoholic beverages. The extracts of Pueraria thomsonii had no influence on blood ethanol and acetaldehyde concentration in humans. However, the extracts increased the elimination rate constant of blood acetaldehyde, although they had no effect on the elimination of blood ethanol in humans. These results suggest that Pueraria thomsonii promotes the elimination of blood acetaldehyde in humans. The present study clinically suggests that a modest stimulatory effect of Pueraria thomsonii on the elimination of blood acetaldehyde may passively mitigate acetaldehyde toxicity, such as flushing, palpitation, headache, etc., associated with excessive alcohol intake.
 ...
PMID:Pharmacological studies on Puerariae Flos. IV: Effects of Pueraria thomsonii dried flower extracts on blood ethanol and acetaldehyde levels in humans. 1239 16

The role of genetic polymorphisms in modulating xenobiotic metabolism and susceptibility to cancer and other health effects has been suggested in numerous studies. However, risk assessments have generally not used this information to characterize population variability or adjust risks for susceptible subgroups. This paper focuses upon the aldehyde dehydrogenase-2 (ALDH2) system because it exemplifies the pivotal role genetic polymorphisms can play in determining enzyme function and susceptibility. Allelic variants in ALDH2 cause decreased ability to clear acetaldehyde and other aldehyde substrates, with homozygous variants (ALDH2*2/2) having no activity and heterozygotes (ALDH2*1/2) having intermediate activity relative to the predominant wild type (ALDH2*1/1). These polymorphisms are associated with increased buildup of acetaldehyde following ethanol ingestion and increased immediate symptoms (flushing syndrome) and long-term cancer risks. We have used Monte Carlo simulation to characterize the population distribution of ALDH2 allelic variants and inter-individual variability in aldehyde internal dose. The nonfunctional allele is rare in most populations, but is common in Asians such that 40% are heterozygotes and 5% are homozygote variants. The ratio of the 95th or 99th percentiles of the Asian population compared to the median of the U.S. population is 14- to 26-fold, a variability factor that is larger than the default pharmacokinetic uncertainty factor (3.2-fold) commonly used in risk assessment. Approaches are described for using ALDH2 population distributions in physiologically based pharmacokinetic-Monte Carlo refinements of risk assessments for xenobiotics which are metabolized to aldehyde intermediates (e.g., ethanol, toluene, ethylene glycol monomethyl ether).
 ...
PMID:Population distribution of aldehyde dehydrogenase-2 genetic polymorphism: implications for risk assessment. 1247 14

Alcoholic beverages are causally related to cancer of the oral cavity, pharynx, larynx and esophagus. Ethanol is oxidized to acetaldehyde and then to acetate by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), both of which have genetic polymorphisms. A review of case-control studies of the effects of ALDH2, ADH2 and ADH3 genotypes shows consistently positive associations between inactive heterozygous ALDH2 and the less-active ADH2 genotypes and the risk for esophageal cancer in East Asian heavy drinkers and this enzyme-related vulnerability may extend to light-to-moderate drinkers. Some studies suggest similar associations with the risk for head and neck cancer in moderate-to-heavy-drinking Japanese. An established carcinogen in experimental animals, acetaldehyde can interact with human DNA. ALDH2-associated cancer susceptibility fits into a scenario in which acetaldehyde plays a critical role in the development of human cancer. Alcohol flushing and drinking behavior may partly explain this carcinogenic effect in carriers of less-active ADH2 genotypes. Whether the ADH3 genotype influences head and neck cancer risk in Western nations is controversial. Professional and public education about risky conditions connected to the ALDH2 and ADH2 genotypes and environmental factors is important in a new strategic approach to the prevention of alcohol-related cancers in East Asians. The use of simple tests to identify inactive ALDH2 on the basis of alcohol flushing responses could benefit many people, by helping them to identify their own cancer risks. Such testing could also help clinicians diagnose esophageal cancer earlier, through the use of endoscopic screening in the high-risk population.
 ...
PMID:Genetic polymorphisms of alcohol and aldehyde dehydrogenases and risk for esophageal and head and neck cancers. 1267 87

Alcoholic drinks are capable of triggering a wide range of allergic and allergic-like responses, including rhinitis, itching, facial swelling, headache, cough and asthma. Limited epidemiological data suggests that many individuals are affected and that sensitivities occur to a variety of drinks, including wine, beer and spirits. In surveys of asthmatics, over 40% reported the triggering of allergic or allergic-like symptoms following alcoholic drink consumption and 30 - 35% reported worsening of their asthma. Sensitivity to ethanol itself can play a role in triggering adverse responses, particularly in Asians, which is due mainly to a reduced capacity to metabolize acetaldehyde. In Caucasians, specific non-alcohol components are the main cause of sensitivities to alcoholic drinks. Allergic sensitivities to specific components of beer, spirits and distilled liquors have been described. Wine is clearly the most commonly reported trigger for adverse responses. Sensitivities to wine appear to be due mainly to pharmacological intolerances to specific components, such as biogenic amines and the sulphite additives. Histamine in wine has been associated with the triggering of a wide spectrum of adverse symptoms, including sneezing, rhinitis, itching, flushing, headache and asthma. The sulphite additives in wine have been associated with triggering asthmatic responses. Clinical studies have confirmed sensitivities to the sulphites in wine in limited numbers of individuals, but the extent to which the sulphites contribute to wine sensitivity overall is not clear. The aetiology of wine-induced asthmatic responses may be complex and may involve several co-factors.
 ...
PMID:Allergic and asthmatic reactions to alcoholic drinks. 1274 10

Enzymes encoded by two gene families, alcohol dehydrogenase ( ADH) and aldehyde dehydrogenase ( ALDH), mediate alcohol metabolism in humans. Allelic variants have been identified that alter metabolic rates and influence risk for alcoholism. Specifically, ADH1B*47His (previously ADH2-2) and ALDH2-2 have been shown to confer protection against alcoholism, presumably through accumulation of acetaldehyde in the blood and a resultant 'flushing response' to alcohol consumption. In the current study, variants at ADH1B (previously ADH2), ADH1C (previously ADH3), and ALDH2 were assayed in DNA extracts from participants belonging to a Southwest American Indian tribe ( n=490) with a high prevalence of alcoholism. Each subject underwent a clinical interview for diagnosis of alcohol dependence, as well as evaluation of intermediate phenotypes such as binge drinking and flushing response to alcohol consumption. Detailed haplotypes were constructed and tested against alcohol dependence and related intermediate phenotypes using both association and linkage analysis. ADH and ALDH variants were also assayed in three Asian and one African population (no clinical data) in order to provide an evolutionary context for the haplotype data. Both linkage and association analysis identified several ADH1C alleles and a neighboring microsatellite marker that affected risk of alcohol dependence and were also related to binge drinking. These data strengthen the support for ADH as a candidate locus for alcohol dependence and suggest further productive study.
 ...
PMID:Allelic variation at alcohol metabolism genes ( ADH1B, ADH1C, ALDH2) and alcohol dependence in an American Indian population. 1288

Early esophageal squamous cell carcinoma detected by esophageal iodine staining can be easily treated by endoscopic mucosectomy, and identifying its predictors is important in better selecting candidates to screen for this high-mortality cancer. The common etiologies of elevated mean corpuscular volume (MCV) and esophageal cancer, including folate deficiency, smoking, drinking and high acetaldehyde exposure, suggest testing MCV as such a predictor. Japanese alcoholic men with (n = 65) and without (n = 206) esophageal squamous cell carcinomas, excluding those with liver cirrhosis, were assessed for MCV within 7 days of their last drink, alone or in combination with findings from either the alcohol flushing questionnaire or genotyping to identify inactive aldehyde dehydrogenase-2 (ALDH2*1/2*2) and the less-active form of alcohol dehydrogenase-2 (ADH2*1/2*1), which pose risks for esophageal squamous cell carcinoma. MCV was higher in cancer patients than in the control group. MCV was higher in both groups in those who were heavier smokers, had lower body mass index (BMI), experienced alcohol flushing, and had ALDH2*1/2*2. After adjusting for age, drinking and smoking habits, BMI and ALDH2/ADH2 genotypes, macrocytosis of MCV > or =106 fl was associated with increased risk for esophageal cancer (OR = 2.75). Men with both MCV > or =106 fl and alcohol flushing had an even higher cancer risk (OR = 5.51). The combinations of MCV > or =106 fl with ALDH2*1/2*2 or ADH2*1/2*1 alone, and both ALDH2*1/2*2 and ADH2*1/2*1 (ORs = 11.44, 21.22 and 319.7, respectively) showed consistently higher risk than the corresponding group with MCV <106 fl (ORs = 7.24, 4.71 and 27.01, respectively). In conclusion, MCV measurement, alone or in combination with the markers of alcohol sensitivity, provides a new means of predicting risk for esophageal squamous cell carcinoma in Japanese alcoholic men.
 ...
PMID:Macrocytosis, a new predictor for esophageal squamous cell carcinoma in Japanese alcoholic men. 1294 54

An atypical allele (ALDH2*2) in low K(m) aldehyde dehydrogenase (ALDH2), which is highly prevalent in Asians, may influence drinking behavior because of higher production of acetaldehyde in the liver. High alcohol sensitivity such as flushing after drinking has been shown to be mainly due to the atypical ALDH2 genotypes. The atypical allele is associated with alcohol-induced liver injury and some cancers. Recently, the researches on the polymorphisms not only in the gene itself but also its frequencies in different Asian populations have been made great progress. Three factors, including different sex, age and geography, were also analyzed with the genotypes of ALDH2 in Chinese populations.
 ...
PMID:[Aldehyde dehydrogenase (ALDH2) polymorphism and drinking behavior]. 1563 99

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.
 ...
PMID:Association of ALDH2 polymorphism with sensitivity to acetaldehyde-induced micronuclei and facial flushing after alcohol intake. 1584 Apr 30


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>