03 May 2018 In Cancer
Several scientific and clinical studies have shown an association between chronic alcohol consumption and the occurrence of cancer in humans. The mechanism for alcohol-induced carcinogenesis has not been fully understood, although plausible events include genotoxic effects of acetaldehyde, cytochrome P450 2E1 (CYP2E1)-mediated generation of reactive oxygen species, aberrant metabolism of folate and retinoids, increased estrogen, and genetic polymorphisms. Here, we summarize the impact of alcohol drinking on the risk of cancer development and potential underlying molecular mechanisms. The interactions between alcohol abuse, anti-tumor immune response, tumor growth, and metastasis are complex. However, multiple studies have linked the immunosuppressive effects of alcohol with tumor progression and metastasis. The influence of alcohol on the host immune system and the development of possible effective immunotherapy for cancer in alcoholics are also discussed here. The conclusive biological effects of alcohol on tumor progression and malignancy have not been investigated extensively using an animal model that mimics the human disease. This review provides insights into cancer pathogenesis in alcoholics, alcohol and immune interactions in different cancers, and scope and future of targeted immunotherapeutic modalities in patients with alcohol abuse
03 May 2018 In Cancer
Several scientific and clinical studies have shown an association between chronic alcohol consumption and the occurrence of cancer in humans. The mechanism for alcohol-induced carcinogenesis has not been fully understood, although plausible events include genotoxic effects of acetaldehyde, cytochrome P450 2E1 (CYP2E1)-mediated generation of reactive oxygen species, aberrant metabolism of folate and retinoids, increased estrogen, and genetic polymorphisms. Here, we summarize the impact of alcohol drinking on the risk of cancer development and potential underlying molecular mechanisms. The interactions between alcohol abuse, anti-tumor immune response, tumor growth, and metastasis are complex. However, multiple studies have linked the immunosuppressive effects of alcohol with tumor progression and metastasis. The influence of alcohol on the host immune system and the development of possible effective immunotherapy for cancer in alcoholics are also discussed here. The conclusive biological effects of alcohol on tumor progression and malignancy have not been investigated extensively using an animal model that mimics the human disease. This review provides insights into cancer pathogenesis in alcoholics, alcohol and immune interactions in different cancers, and scope and future of targeted immunotherapeutic modalities in patients with alcohol abuse
02 August 2016 In Liver Disease

BACKGROUND & AIMS: Studies assessing alcohol as a population-level risk factor for cirrhosis, typically focus on per capita consumption. However, clinical studies indicate that daily intake is a strong predictor of alcoholic cirrhosis. We aimed to identify the determinants of alcohol's contribution to the global cirrhosis burden and to evaluate the influence of daily drinking on a population level.

METHODS: We performed a comprehensive analysis of the WHO 2014 Global Status Report on Alcohol and Health. We categorized countries by heavy or moderate drinking based on daily consumption, using U.S. Department of Agriculture definitions of heavy drinking. Additional data on cirrhosis cofactors were also obtained. Uni- and multivariate models were fitted to identify independent predictors of the alcohol-attributable fraction of cirrhosis.

RESULTS: The WHO 2014 Report found that half of cirrhosis mortality worldwide is attributable to alcohol, approximating 60% in North America and Europe. In an integrative multivariate model, the designation of countries by moderate or heavy daily drinking had the strongest influence on the weight of alcohol in the cirrhosis burden. The relative contribution from alcohol increased by 11% with a transition from the moderate to heavy classification (p<0.001). Importantly, drinking patterns such as heavy episodic drinking and the type of alcohol did not independently predict the alcohol-attributable fraction of cirrhosis.

CONCLUSIONS: Heavy daily drinking on a population level significantly influences the weight of alcohol in the cirrhosis burden. Reducing heavy drinking should be considered as an important target for public health monitoring and policies.

LAY SUMMARY: We carried out an analysis of the WHO 2014 Global Status Report on Alcohol and Health, and categorized countries by their level of drinking (heavy or moderate). We found that half of the global cirrhosis cases, and 60% in both North America and Europe are associated with alcohol intake. We concluded that on a population level heavy daily drinking significantly influences the impact of alcohol on the cirrhosis burden.

11 May 2015 In Liver Disease

BACKGROUND: Alcohol abuse represents the most common cause of liver disease in the Western countries. Pre-clinical and clinical studies showed that alcohol consumption affects amount and composition of gut microbiota. Moreover, gut flora plays an important role in the pathogenesis of alcoholic liver injury.

AIM: To review the relationship between alcohol administration and changes on gut microbiota, its involvement in the pathogenesis of alcoholic liver disease, and how gut microbiota modulation could be a target for the treatment of alcoholic liver disease.

METHODS: Articles were identified using the PubMed database with the search terms 'Alcohol', 'Gut Microbiota', 'Alcoholic liver disease', 'Probiotic', 'Prebiotic', 'Symbiotic' and 'Antibiotic'. English-language articles were screened for relevance. Full review of publications for the relevant studies was conducted, including additional publications that were identified from individual article reference lists.

RESULTS: Alcohol abuse induces changes in the composition of gut microbiota, although the exact mechanism for this alteration is not well known. The translocation of bacterial products into the portal blood appears to play a key role in alcohol-induced liver damage. Several studies show that the modulation of gut microbiota seem to be a promising strategy to reduce alcohol-induced liver injury.

CONCLUSIONS: Further studies are needed to better understand the relationship between alcohol administration and changes in gut microbiota, and its involvement in alcoholic liver disease. Moreover larger studies are needed to confirm the preliminary results on the therapeutic effects of gut microbiota modulation.

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