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Antioxidants (Basel, Switzerland) Jul 2022Alcohol use disorder (AUD) is a highly prevalent, comorbid, and disabling disorder. The underlying mechanism of ethanol neurotoxicity and the involvement of oxidative... (Review)
Review
Alcohol use disorder (AUD) is a highly prevalent, comorbid, and disabling disorder. The underlying mechanism of ethanol neurotoxicity and the involvement of oxidative stress is still not fully elucidated. However, ethanol metabolism has been associated with increased oxidative stress through alcohol dehydrogenase, the microsomal ethanol oxidation system, and catalase metabolic pathways. We searched the PubMed and genome-wide association studies (GWAS) catalog databases to review the literature systematically and summarized the findings focusing on AUD and alcohol abstinence in relation to oxidative stress. In addition, we reviewed the ClinicalTrials.gov resource of the US National Library of Medicine to identify all ongoing and completed clinical trials that include therapeutic interventions based on antioxidants. The retrieved clinical and preclinical studies show that oxidative stress impacts AUD through genetics, alcohol metabolism, inflammation, and neurodegeneration.
PubMed: 35883865
DOI: 10.3390/antiox11071374 -
Bioscience Reports Apr 2019Alcohol consumption has been established to be a major factor in the development and progress of cancer. Genetic polymorphisms of alcohol-metabolism genes result in... (Meta-Analysis)
Meta-Analysis
Alcohol consumption has been established to be a major factor in the development and progress of cancer. Genetic polymorphisms of alcohol-metabolism genes result in differences between individuals in exposure to acetaldehyde, leading to possible carcinogenic effects. Arg47His (rs1229984 G > A) in have been frequently studied for its potential effect on carcinogenesis. However, the findings are as yet inconclusive. To gain a more precise estimate of this potential association, we conducted a meta-analysis including 66 studies from 64 articles with 31999 cases and 50964 controls. The pooled results indicated that Arg47His polymorphism is significantly associated with the decreased risk of overall cancer (homozygous model, odds ratio (OR) = 0.62, 95% confidence interval (CI) = 0.49-0.77; heterozygous model, OR = 0.71, 95% CI = 0.60-0.84; recessive model, OR = 0.83, 95% CI = 0.76-0.91; dominant model, OR = 0.62, 95% CI = 0.53-0.72; and allele comparison, OR = 0.82, 95% CI = 0.75-0.89). Stratified analysis by cancer type and ethnicity showed that a decreased risk was associated with esophageal cancer and head and neck cancer amongst Asians. In conclusion, our meta-analysis suggested that Arg47His polymorphism was significantly associated with decreased overall cancer risk. These findings need further validation in large multicenter investigations.
Topics: Alcohol Dehydrogenase; Carcinogenesis; Esophageal Neoplasms; Head and Neck Neoplasms; Models, Genetic; Neoplasm Proteins; Neoplasms; Polymorphism, Genetic
PubMed: 30872408
DOI: 10.1042/BSR20181915 -
Bulletin of the World Health... May 2015To refine estimates of the burden of alcohol-related oesophageal cancer in Japan. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To refine estimates of the burden of alcohol-related oesophageal cancer in Japan.
METHODS
We searched PubMed for published reviews and original studies on alcohol intake, aldehyde dehydrogenase polymorphisms, and risk for oesophageal cancer in Japan, published before 2014. We conducted random-effects meta-analyses, including subgroup analyses by aldehyde dehydrogenase variants. We estimated deaths and loss of disability-adjusted life years (DALYs) from oesophageal cancer using exposure distributions for alcohol based on age, sex and relative risks per unit of exposure.
FINDINGS
We identified 14 relevant studies. Three cohort studies and four case-control studies had dose-response data. Evidence from cohort studies showed that people who consumed the equivalent of 100 g/day of pure alcohol had an 11.71 fold, (95% confidence interval, CI: 2.67-51.32) risk of oesophageal cancer compared to those who never consumed alcohol. Evidence from case-control studies showed that the increase in risk was 33.11 fold (95% CI: 8.15-134.43) in the population at large. The difference by study design is explained by the 159 fold (95% CI: 27.2-938.2) risk among those with an inactive aldehyde dehydrogenase enzyme variant. Applying these dose-response estimates to the national profile of alcohol intake yielded 5279 oesophageal cancer deaths and 102,988 DALYs lost - almost double the estimates produced by the most recent global burden of disease exercise.
CONCLUSION
Use of global dose-response data results in an underestimate of the burden of disease from oesophageal cancer in Japan. Where possible, national burden of disease studies should use results from the population concerned.
Topics: Alcohol Dehydrogenase; Alcohol Drinking; Esophageal Neoplasms; Ethanol; Humans; Japan; Quality-Adjusted Life Years; Risk Factors
PubMed: 26229204
DOI: 10.2471/BLT.14.142141 -
PLoS Medicine Mar 2008Alcohol has been reported to be a common and modifiable risk factor for hypertension. However, observational studies are subject to confounding by other behavioural and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alcohol has been reported to be a common and modifiable risk factor for hypertension. However, observational studies are subject to confounding by other behavioural and sociodemographic factors, while clinical trials are difficult to implement and have limited follow-up time. Mendelian randomization can provide robust evidence on the nature of this association by use of a common polymorphism in aldehyde dehydrogenase 2 (ALDH2) as a surrogate for measuring alcohol consumption. ALDH2 encodes a major enzyme involved in alcohol metabolism. Individuals homozygous for the null variant (*2*2) experience adverse symptoms when drinking alcohol and consequently drink considerably less alcohol than wild-type homozygotes (*1*1) or heterozygotes. We hypothesise that this polymorphism may influence the risk of hypertension by affecting alcohol drinking behaviour.
METHODS AND FINDINGS
We carried out fixed effect meta-analyses of the ALDH2 genotype with blood pressure (five studies, n = 7,658) and hypertension (three studies, n = 4,219) using studies identified via systematic review. In males, we obtained an overall odds ratio of 2.42 (95% confidence interval [CI] 1.66-3.55, p = 4.8 x 10(-6)) for hypertension comparing *1*1 with *2*2 homozygotes and an odds ratio of 1.72 (95% CI 1.17-2.52, p = 0.006) comparing heterozygotes (surrogate for moderate drinkers) with *2*2 homozygotes. Systolic blood pressure was 7.44 mmHg (95% CI 5.39-9.49, p = 1.1 x 10(-12)) greater among *1*1 than among *2*2 homozygotes, and 4.24 mmHg (95% CI 2.18-6.31, p = 0.00005) greater among heterozygotes than among *2*2 homozygotes.
CONCLUSIONS
These findings support the hypothesis that alcohol intake has a marked effect on blood pressure and the risk of hypertension.
Topics: Alcohol Dehydrogenase; Alcohol Drinking; Blood Pressure; Genetic Predisposition to Disease; Humans; Hypertension; Male
PubMed: 18318597
DOI: 10.1371/journal.pmed.0050052