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Salem Health: Cancer Alcohol, Alcoholism & Cancer Category: Carcinogens and suspected carcinogens Definition Alcohol is a chemical that is generated during fermentation of sugar. Ethyl alcohol is the specific chemical that is generally referred to as alcohol. Alcohol is the most commonly used intoxicating agent around the world. Alcoholism is a phenomenon of continuous intake of alcohol, with a compulsive need to consume it (also called alcohol-dependence syndrome). Cancer has been linked to several cancers but a direct causal relationship between the two has not been established. Alcohol as a Carcinogen Intake of alcohol is considered a risk factor for developing various kinds of cancers, and therefore, alcohol has been classified as a carcinogen. Ethyl alcohol, the form in which alcohol is commonly consumed, undergoes an array of metabolic changes when ingested. The main enzymes that are involved in metabolism of alcohol are alcohol dehydrogenase and aldehyde dehydrogenase. A small amount (approximately 10 percent) is metabolized by microsomal cytochrome P4502E1 (CYP2E1). Alcohol dehydrogenase converts about 80 percent of ethanol to acetaldehyde. Acetaldehyde is a mutagen and a carcinogen and is considered a risk factor in many cancers of the upper gastrointestinal tract. Acetaldehyde is implicated in a variety of processes such as inflammation of the tracheal epithelium, delaying of cell cycle progression, induction of apoptosis, chromosomal damages and aberrations, and sister chromatid exchanges. Much of the carcinogenic effect of alcohol is attributed to this single metabolite. Direct association between the concentration of acetaldehyde in saliva and development of cancer has been reported. Acetaldehyde covalently bonds with deoxyribonucleic acid (DNA) and forms structures called DNA-adducts. The most common DNA-acetaldehyde adduct is N2-ethyl-dG, which is not mutagenic. Acetaldehyde also induces the formation of the mutagenic DNA adduct called Cr-PdG (alpha-methyl-gamma-hydroxy-1, N2-propano-2'-deoxyguanosine). Polyamines are one of the basic molecules essential for cells and are implicated in cell growth and differentiation, nucleic acid synthesis, and protection against oxidative damage. Polyamines facilitate acetaldehyde-induced formation of Cr-PdG adducts. Cr-PdG adducts are highly mutagenic and interfere with DNA replication and repair, inducing cancer formation. Polyamines also react with acetaldehyde and form crotonaldehyde, which is highly carcinogenic. Response to alcohol is individualistic and differs between people and races. This is because of polymorphisms in the genes for the enzymes alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Presence of the ALDH2*1/2 allele significantly increases the risk of upper aerodigestive tract cancer. In addition to these enzymes, oral bacteria also generate acetaldehyde. High amounts of acetaldehyde are detected in saliva after alcohol consumption. Saliva is directly in contact with the upper aerodigestive tract, and this contact is considered a possible mechanism for its carcinogenic effects. Alcohol and Breast Cancer Alcohol is one of the most ancient intoxicants known to humankind. Consuming one or two drinks a day is not just common but is also a social custom in many cultures. However, research suggests that even one or two drinks a day could put women at a greater risk for developing breast cancer. A study conducted at the National Cancer Institute tested postmenopausal women for differences in hormone levels after alcohol consumption (15 or 30 grams of alcohol per day) for eight weeks. Results showed a significant elevation of estrone sulfate (an estrogen metabolite) and the hormone, DHEAS (dihdro epiandrosterone sulfate). DHEAS is secreted by the adrenal glands, and increased levels of DHEAS indicate induction of a process called adrenal steroidogenesis, reflecting stimulation of the hypothalamic-pituitary-adrenal axis in the brain as a response to alcohol consumption. Alcohol and Liver Cancers Excessive consumption of alcohol leads to alcohol liver disease. One type of alcohol liver disease is called alcoholic cirrhosis of the liver, a condition in which normal liver tissue is completely destroyed. Cirrhosis of liver is considered the primary risk factor for development of hepatocellular carcinoma (liver cancer). Even though alcohol does not seem to cause liver cancer directly, there is a strong association between alcohol and liver cancer. Alcohol and Other Cancers Drinking two or more drinks per day increases the risk of oral and upper gastrointestinal tract (GI) cancers in both men and women. Alcohol-related cancers include those of the mouth, esophagus, and larynx. Drinking alcohol together with smoking increases the risk of developing cancer more than by drinking alone. Alcohol is addictive, and alcoholism leads to enhanced tolerance levels, loss of control, cravings for alcohol, and an inability to stop drinking even when people wish to stop or need to stop for their health. Evidence shows that the nutritional status of the body is also affected by alcohol. Perspectives and Progress According to World Health Organization statistics, alcohol is responsible for about 1.8 million deaths a year, and alcohol-related cancer is the most common cause of these deaths. Some 3.6 percent of all cancer-related deaths are caused by chronic alcohol consumption. Education to make people aware of the link between alcohol consumption and cancer should aid in prevention of such cancers. Geetha Yadav, Ph.D. For Further InformationCho, Chi Hin, and Vishnudutt Purohit, eds. Alcohol, Tobacco, and Cancer. New York: Karger, 2006. Dorgan, J. F., et al. "Serum Hormones and the Alcohol-Breast Cancer Association in Postmenopausal Women." Journal of the National Cancer Institute 93 (2001): 710-715. Seitz, H. K., B. Maurer, and F. Stickel. "Alcohol Consumption and Cancer of the Gastrointestinal Tract." Digestive Diseases 23 (2005): 297-303. Seitz, H. K., and F. Stickel. "Molecular Mechanisms of Alcohol-Mediated Carcinogenesis. Nature Reviews 7 (2007): 599-612. Yirmiya, Raz, and Anna N. Taylor, eds. Alcohol, Immunity, and Cancer. Boca Raton, La.: CRC Press, 1993. Other Resources American Cancer Society Alcohol and Cancer http://www.cancer.org/docroot/PRO/content/PRO_1_1x_Alcohol.pdf.asp?sitearea=PRO National Cancer Institute Alcohol Consumption http://progressreport.cancer.gov/doc_detail.asp?pid=1&did=2007&chid=71&coid=706&mid= See Also breast cancer; esophageal cancer; gastrointestinal cancers; hepatomegaly; laryngeal cancer; liver cancers; oral and oropharyngeal cancers; polyps; stomach cancer; throat cancers |
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