Genetic polymorphisms of alcohol metabolising enzymes: their role in susceptibility to oesophageal cancer.
BACKGROUND
Alcohol is a major risk factor for susceptibility to oesophageal cancer in the South African population. The role of polymorphisms in alcohol metabolising enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH2) in predisposition of this population to oesophageal cancer is unknown. Alcohol metabolising enzymes exhibit polymorphisms that result in variant alleles with either increased or decreased activity.


METHODS
The role of these polymorphisms in increased risk of oesophageal cancer was investigated in 238 patients and 268 controls from Black and Mixed Ancestry South Africans, using the PCR/RFLP technique.


RESULTS
The ADH3*2/*2 genotype was significantly associated with increased risk for oesophageal cancer amongst Black subjects (odds ratio, 2.19; p=0.004). The low activity ALDH2*2 allele was significantly associated with increased risk for oesophageal cancer amongst the Black subjects (odds ratio, 2.35; p=0.0084).


CONCLUSIONS
It was observed that ADH variants, ADH2*1 and ADH3*2, were associated with increased risk for oesophageal cancer, possibly due to the tolerance of the carriers of these alleles to alcohol consumption compared to those with high activity alleles (ADH2*2 and ADH2*3) which are associated with higher production of the unpleasant acetaldehyde intermediate.
Li
Dong-Ping
DP
Department of Molecular and Cell Biology, University of Witwatersrand, Johannesburg, South Africa.
Dandara
Collet
C
Walther
Gabi
G
Parker
M Iqbal
MI
D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000483:Alleles; D044383:Black People / Q000235:genetics; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D012907:Smoking; D013019:South Africa / Q000208:ethnology
D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase