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Hepatic and Extrahepatic Malignancies in Alcoholic Liver Disease

  • Samir ZakhariEmail author
  • Svetlana Radaeva
  • Vasilis Vasiliou

Abstract

Alcohol consumption has been identified in epidemiological studies as a risk factor for cancer of the esophagus, pharynx, larynx, and oral cavity (collectively known as upper aerodigestive tract, UADT) and breast, as well as liver cancer. While inconsistent relationship between alcohol drinking and UADT cancer mortality was reported, heavy alcohol consumption could increase UADT cancer mortality, especially if combined with tobacco use. Epidemiological studies on alcohol and breast cancer are also inconsistent. The variability in outcomes in alcohol and cancer epidemiological studies stems from: (1) studies rely on self-report to determine the amount of alcoholic beverage consumed, which introduces “recall bias”; (2) cancer develops over a long period and epidemiological studies that capture current or recent alcohol consumption after clinical diagnosis cannot correlate that with carcinogenesis; (3) cancer is a multifactorial disease that culminates by complex interactions of numerous risk factors—genetic and environmental—over time. Thus, epidemiological studies cannot determine cause-and-effect relationships and are unable to give biological and clinical insights into carcinogenesis. This review focuses on hepatocellular carcinoma (HCC) and enumerates known plausible mechanisms of hepatocarcinogenesis.

Chronic heavy drinking invariably results in a spectrum of alcoholic liver disease terminating in cirrhosis in only ~10 %. Among patients with cirrhosis, about 1–2 % develops HCC. Other comorbid conditions such as HBV or HCV infection, obesity, or hemochromatosis and lifestyle factors such as smoking or ingestion of food contaminated with aflatoxin can exacerbate liver damage and amplify HCC.

This review discusses plausible mechanisms for HCC genesis due to heavy alcohol consumption including: (1) alcohol metabolism, which results in acetaldehyde generation and formation of DNA adducts, reactive oxygen species formation, changes in redox state of hepatocytes, and derangement of metabolic pathways, especially retinoic acid synthesis and transport; (2) epigenetic effects of alcohol especially on the DNA methylation, histone modification, and miRNA availability and function; (3) circadian rhythm perturbation; (4) immune system modifications; and (5) angiogenesis.

Keywords

Alcohol metabolism Cirrhosis Hepatocellular carcinoma Metabolism Epigenetics Reactive oxygen species Retinoic acid Oxidative stress Immune dysfunction Circadian rhythm Angiogenesis 

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Samir Zakhari
    • 1
    Email author
  • Svetlana Radaeva
    • 2
  • Vasilis Vasiliou
    • 3
  1. 1.Office of Science, DISCUSWashington, DCUSA
  2. 2.Division of Metabolism and Health EffectsNational Institute on Alcohol Abuse and AlcoholismBethesdaUSA
  3. 3.Department of Environmental Health SciencesYale School of Public HealthNew HavenUSA

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