The polymorphic enzyme alcohol dehydrogenase (ADH) catalyses the conversion of ethanol
into the carcinogenic metabolite acetaldehyde which is partly excreted into the urine.
Objectives of this pilot study are to determine whether this polymorphism may be related
to bladder cancer and whether it modifies the relation between alcohol intake and
120 bladder cancer patients and 133 convenience controls were recruited at the University
Medical Centre Nijmegen. A self-administered questionnaire was used to assess alcohol
intake and potential confounders. DNA was isolated from peripheral blood, and ADH3
genotype was determined using PCR/RFLP. People with the ADH3 genotype gamma1gamma1
were compared to people with other ADH3 genotypes. Above moderate drinkers (>14 glasses
of alcohol per week) were compared to moderate drinkers. Odds ratios (ORs) and 95%
confidence intervals were computed using logistic regression analyses.
After correction for sex, age and smoking, ORs for ADH3 genotype and alcohol intake
were 2.10 (1.05-4.22) and 1.21 (0.60-2.44), respectively. Moderate drinkers with the
'high-risk' (gamma1gamma1) ADH3 genotype appeared to have a threefold higher risk
of bladder cancer compared to moderate drinkers with a 'low-risk' (gamma1gamma2 or
gamma2gamma2) genotype. Surprisingly, the ORs for above moderate drinkers with the
low-risk genotype (1.95; 95% CI: 0.85-4.48) and with the high-risk genotype (2.18;
95% CI: 0.82-5.77) were almost similar, suggesting no interaction.
ADH3 genotype is a possible risk factor for bladder cancer. Although moderate drinkers
with the gamma1gamma1 genotype seem to have the highest risk, we did not get a clear
indication that ADH3 genotype modifies the relationship between alcohol intake and