Alcohol and Cancer

Abstract

Epidemiological data have identified chronic alcohol consumption as a significant risk factor for upper alimentary tract cancer, including cancer of the oropharynx, larynx and the oesophagus and of the liver. The increased risk attributable to alcohol consumption of cancer in the large intestine and in the breast is much smaller. However, although the risk is lower, carcinogenesis can be enhanced with relatively low daily doses of ethanol. Considering the high prevalence of these tumours, even a small increase in cancer risk is of great importance, especially in those individuals who exhibit a higher risk for other reasons. The epidemiological data on alcohol and other organ cancers is controversial and there is at present not enough evidence for a significant association. Although the exact mechanisms by which chronic alcohol ingestion stimulates carcinogenesis are not known, experimental studies in animals support the concept that ethanol is not a carcinogen but under certain experimental conditions is a cocarcinogen and/or tumour promoter. The metabolism of ethanol leads to the generation of acetaldehyde (AA) and free radicals. Evidence has accumulated that acetaldehyde is predominantly responsible for alcohol associated carcinogenesis. Acetaldehyde is carcinogenic and mutagenic, binds to DNA and proteins, destructs folate and results in secondary hyperproliferation. Acetaldehyde is produced by tissue alcohol hydrogenases, cytochrome P 4502E1 and through bacterial oxidative metabolism in the upper and lower gastrointestinal tract. Its generation or its degradation is modulated due to functional polymorphisms of the genes coding for the enzymes. Acetaldehyde can also be produced by oral and faecal bacteria. Smoking, which changes the oral bacterial flora, and poor oral hygiene also increase acetaldehyde. In addition, cigarette smoking and some alcoholic beverages such as calvados contain acetaldehyde. Other mechanisms by which alcohol stimulates carcinogenesis include the induction of cytochrome P-4502E1, which is associated with an enhanced production of free radicals and enhanced activation of various procarcinogens present in alcoholic beverages; in association with tobacco smoke and in diets, a change in the metabolism and distribution of carcinogens; alterations in cell cycle behaviour such as cell cycle duration leading to hyperproliferation; nutritional deficiencies, such as methyl-, vitamin E-, folate-, pyridoxal phosphate-, zinc- and selenium deficiencies and alterations of the immune system eventually resulting in an increased susceptibility to certain virus infections such as hepatitis B virus and hepatitis C virus. In addition, local mechanisms may be of particular importance. Such mechanisms lead to tissue injury such as cirrhosis of the liver, a major prerequisite for hepatocellular carcinoma. Also, an alcohol-mediated increase in oestradiols may be at least in part responsible for breast cancer risk. Thus, all these mechanisms functioning in concert actively modulate carcinogenesis leading to its...

Risk factors and mechanisms of hepatocarcinogenesis with special emphasis on alcohol and oxidative stress

“…Alcohol by itself is not a carcinogen when given to animals (Ketcham et al, 1963). However, alcohol enhances chemically induced hepatocarcinogenesis, especially when nitrosamines are used for tumor induction (Pö schl and Seitz, 2004). Thus, under certain experimental conditions, alcohol may act as a tumor promoter.…”

“…There is increasing evidence that acetaldehyde rather than alcohol itself is responsible for the cocarcinogenic effect of alcohol (Pö schl and Seitz, 2004). Acetaldehyde is highly toxic, mutagenic and carcinogenic.…”

“…The present review focuses on alcohol-related HCC, with special emphasis on oxidative stress. Other alcohol-related mechanisms promoting the development of HCC are outlined elsewhere (Stickel et al, 2002;Pö schl and Seitz, 2004;Stickel and Seitz, 2004;McKillop and Schrum, 2005).…”

Southern Europe as an example of interaction between various environmental factors: a systematic review of the epidemiologic evidence

“…The pathogenetic mechanisms whereby alcohol intake can lead to development of cirrhosis and HCC are discussed in detail in some recent reviews (Poschl and Seitz, 2004;McKillop and Schrum, 2005;Voigt, 2005).…”

Making Sense of Racial Disparities in Gastrointestinal Cancer Mortality

“…For instance, infections with viral hepatitis B and hepatitis C have been associated with increased risk of hepatocellular carcinoma while Helicobacter pylori infection has been associated with increased risk of gastric cancer. Behavioral and lifestyle choices that have been identified as increasing the risk of gastrointestinal cancers include: obesity with colorectal cancer [5,6], smoking with pancreatic cancer [7], and alcohol ingestion with esophageal, pancreatic, and colorectal cancers [8,9]. b) Lack of uptake of preventive care services: Although few cancers have been shown to be amenable to screening, disparities in utilization of screening services and early detection can lead to late-stage presentation of cancers with limited options for cure.…”