Source
Department of Molecular and Cell Biology, University of Witwatersrand, Johannesburg, South Africa.
Abstract
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.