Review Alcohol and Cancer

Epidemiological data haAe identified chronic alcohol col1SLImptim as a 518111 ficant 1'1 k facto' for Li pper alimenllll • tract cancer. including cancer of the oropharynx, lar•nx and the oesophagus and of the li y ei 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 lo•er, carcino,,enesis can he enhanced with relativ^ely low daily doses of ethanol_ Considering the high prev^alence of these tumours, even a small increase in cancer risk is of great i mportance, especially in those individuals who exhibit a higher risk for other reasons.'I'he epidemiological data on alcohol and other organ cancers is contl'over ial and there is at present not enough eV -deuce for a sign ilic nt awociation. Although the exact Illeclianisms b y which chronic alcohol Ingestion stim1I latex carciI1lgellesis are not klll n. experimental SLLIdieS in animals support the concept that ethanol is not a carcinogen but under certain experimental conditions is a cocalcinogen and/or tumour pronloler_'I'he metabolism of ethanol leads to the generation of acetaldehyde (;AAI and free radicals_ Evidence has accumulated that acetaldehyde is predominantly responsible for alcohol associated caicinogenesis. Acetaldehyde is carcinogenic and mutagenic, binds to DNA and proteins, destu'ucts folate and results in secondary hoperproh feratioii. Acetaldeh y de is produced by tiSSLIe alcohol hxdroge111LSes. cytochl'ome P 4N)2LI and through bacterial oxidative metabolism in the Lipper and lower gastrointestinal trac t. Its generation or its degradation is modulated due to functional polymorphi ms of the genes coding for the envynles_ Acetaldehyde can also he pro lured by oral and faecal hacteria_ 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 c ucinogenesis include the induction of cytochronle Y -4502E l, which is a ociated with all enhanced production of free radicals and enhanced activation Of VLll'IOLIS p1' )carcinogen present in alcoho lic beVerages: in a ociation with tobacco smoke and in diets. a change in the metabolism and diSti'1bL111011 Of carcinoge11S: alterations in cell cycle belia 'iOLII SLICK LIS cell c cIc dLII atiill leading to 11 pe 'hl'OIlf21'1111011: nutritional deficiencies, SLICK as meth y l-. vitamin E-. filaie-. iyridoxlll phosphate-, zincand selenium deficiencies and alterations of the immune system eventually resulting in an increased Susceptibility to certain v irus infections Such aS hepatitis B virus and hepatitis C v irus. In addition, local mech a lisnls may he of particular impo rtance. Such Illechanisms lead to tiSSLIe injur y SLICK LaS Cil'1'hOSiS Of the liver, a Il1L1j01' pi'ere(iui its f01' hep ato Cel ILI lilt' carcinoma. Also, an arc oliol-mediated increase 111 )e tradiok may be at least in part responsible f01' breast cancel' 1 '1 k. ThL IS. all these mechanism functioning ill Conce1't arilAelV' modulate Cal'c1110ge11eSi leading to its S tilIILI latioii.