Roles of alcohol and tobacco exposure in the development of hepatocellular carcinoma

Abstract

The purpose of this report is to summarize the roles of alcohol and tobacco exposure in the development of hepatocellular carcinoma (HCC). Chronic heavy alcohol exposure is a major risk factor for HCC, which is the most frequent type of liver cancer. Alcohol ingestion may initiate and or promote the development of HCC by: 1) acetaldehyde-DNA adduct formation; 2) cytochrome P4502E1-associated reactive oxygen species (ROS) generation, lipid peroxidation, p53 mutation, and conversion of pro-carcinogens to carcinogens; 3) iron accumulation that leads to ROS generation, lipid peroxidation, p53 mutation, and initiation of inflammatory cascade via nuclear factor-KappaB (NF-kB) activation; 4) glutathione depletion leading to oxidative stress; 5) s-adenosylmethionine (SAM) depletion and associated DNA hypomethylation of oncogenes ; 6) retinoic acid depletion and resultant hepatocyte proliferation via up-regulation of activator protein-1 (AP-1); 7) initiating an inflammatory cascade through increased transfer of endotoxin from intestine to liver, Kupffer cell activation via CD14/toll-like receptor-4 (TLR-4), oxidative stress, NF-kB or early growth response-1(Egr-1) activation, and generation of inflammatory cytokines and chemokines; 8) induction of liver fibrosis; and 9) decreasing the number and/or function of Natural Killer cells. Tobacco exposure is also a risk factor for HCC. It may contribute to the initiation and promotion of HCC due the presence of mutagenic and carcinogenic compounds as well as by causing oxidative stress due to generation of ROS and depletion of endogenous antioxidants. Simultaneous exposure to alcohol and tobacco is expected to promote the development of HCC in an additive and/or synergistic manner.

Risk of Cancer in Patients with Cholecystitis: A Nationwide Population-based Study

“…First, the data about personal characteristics, such as cigarette smoking, body mass index, alcohol consumption, and family history of malignancy were not available in the NHIRD; and this study was unable to evaluate them as the potential confounding factors for specific cancers. 34,[39][40][41][42][43] Second, misclassification or incorrect coding of diseases in the NHIRD is possible. To minimize this bias, we performed a sensitivity analysis by looking only at patients with twice or thrice diagnostic coding of cholecystitis and still obtained similar results.…”

Translational Implications of the Alcohol-Metabolizing Enzymes, Including Cytochrome P450-2E1, in Alcoholic and Nonalcoholic Liver Disease

“…In addition, it is known that there are relatively large individual variations in the rate of ethanol elimination, possibly due to genetic and environmental factors (Li, Yin, Crabb, O'Connor, & Ramchandani, 2001). Furthermore, the liver disease progression can be exacerbated or facilitated especially in the presence of other comorbidity risk factors (Lieber, 2004a), such as hepatitis B or C virus (Mueller, Millonig, & Seitz, 2009;Otani et al, 2005;Rigamonti et al, 2003;Szabo, Saha, & Bukong, 2015;Szabo et al, 2010;Zakhari, 2013), HIV (Fan, Joshi, Koval, & Guidot, 2011;Persidsky et al, 2011), obesity (Cederbaum, 2012a;Hart, Morrison, Batty, Mitchell, & Davey, 2010;Loomba et al, 2013Loomba et al, , 2010, diabetes (Hassan et al, 2002), smoking (Kuper et al, 2000;Purohit, Rapaka, Kwon, & Song, 2013;Salaspuro & Salaspuro, 2004), clinically used drugs (Boelsterli & Lee, 2014;McClain, Kromhout, Peterson, & Holtzman, 1980;Seeff, Cuccherini, Zimmerman, Adler, & Benjamin, 1986), or environmental contaminants such as benzene in gasoline (Kalf, Post, & Snyder, 1987). For instance, people who drink more than 60 g/day are more likely to develop fibrosis, cirrhosis, hepatocellular carcinoma, and ultimately liver failure (Lucey, Mathurin, & Morgan, 2009;.…”

Short-Term Effects of Nose-Only Cigarette Smoke Exposure on Glutathione Redox Homeostasis, Cytochrome P450 1A1/2 and Respiratory Enzyme Activities in Mice Tissues

“…There are a number of tobacco-related active compounds, such as nicotine, NNK, other nitrosamines and aromatic amines and polycyclic aromatic hydrocarbons which are known toxicants and carcinogens [3,4,5]. Cigarette smoke (CS) and its main component nicotine and NNK have also been shown to induce cytochrome P450 activities in the liver and other tissues [6,7].…”