The role of acetaldehyde in upper digestive tract cancer in alcoholics.
Chronic excessive alcohol consumption is the strongest risk factor for upper aerodigestive tract (UADT) cancer. Multiple mechanisms are involved in alcohol-associated cancer development of the UADT, including acetaldehyde (AA) effects. AA is toxic, mutagenic, and carcinogenic. Evidence of the role of AA in alcohol-associated carcinogenesis derived from genetic linkage studies in alcoholics. Polymorphism or mutation in genes coding for AA generation or detoxification enzymes are associated with increased cancer risk. It has been clearly shown in Asians that individuals carrying the acetaldehyde dehydrogenase 2*2 (ALDH2*2) allele have a significantly increased cancer risk when they consume alcohol. In Caucasians, alcohol dehydrogenase 1*1 (ADH1C*1) allele encodes for an alcohol dehydrogenase (ADH) isoenzyme, which produces 2.5 times more AA than the corresponding allele ADH1C*2. The authors found that the ADH1C*1 allele frequency and rate of homozygosity was significantly associated with an increased risk for alcohol-related cancer. AA seems to be an important factor in alcohol-associated carcinogenesis of the UADT.
Seitz
Helmut K
HK
Department of Medicine and Laboratory of Alcohol Research, Liver Disease and Nutrition, Salem Medical Centre, Heidelberg, Germany. helmut.karl.seitz@urz.uni-heidelberg.de
Meier
Patrick
P
D000079:Acetaldehyde / Q000378:metabolism*; D000426:Alcohol Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000437:Alcoholism / Q000150:complications / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D044466:Asian People / Q000235:genetics; D005770:Gastrointestinal Neoplasms / Q000209:etiology / Q000378:metabolism*; D005787:Gene Frequency; D006801:Humans; D011110:Polymorphism, Genetic; D044465:White People / Q000235:genetics
C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000079:Acetaldehyde