3型乙醇脱氢酶（ADH3）与膀胱癌风险

van Dijk B, van Houwelingen K P, Witjes J A, Schalken J A, Kiemeney L A

Department of Urology, University Medical Centre, Nijmegen, The Netherlands.

Eur Urol. 2001 Nov;40(5):509-14. doi: 10.1159/000049827.

OBJECTIVES

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 bladder cancer.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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 bladder cancer.

目的

多态性酶乙醇脱氢酶（ADH）催化乙醇转化为致癌代谢物乙醛，部分乙醛会排泄到尿液中。本初步研究的目的是确定这种多态性是否可能与膀胱癌相关，以及它是否会改变酒精摄入量与膀胱癌之间的关系。

方法

在奈梅亨大学医学中心招募了120名膀胱癌患者和133名便利对照组。使用自填式问卷评估酒精摄入量和潜在混杂因素。从外周血中分离DNA，并使用PCR/RFLP确定ADH3基因型。将ADH3基因型为γ1γ1的人与其他ADH3基因型的人进行比较。将重度饮酒者（每周饮酒超过14杯）与中度饮酒者进行比较。使用逻辑回归分析计算比值比（OR）和95%置信区间。

结果

在对性别、年龄和吸烟进行校正后，ADH3基因型和酒精摄入量的OR分别为2.10（1.05 - 4.22）和1.21（0.60 - 2.44）。与具有“低风险”（γ1γ2或γ2γ2）基因型的中度饮酒者相比，具有“高风险”（γ1γ1）ADH3基因型的中度饮酒者患膀胱癌的风险似乎高出三倍。令人惊讶的是，具有低风险基因型（1.95；95%CI：0.85 - 4.48）和高风险基因型（2.18；95%CI：0.82 - 5.77）的重度饮酒者的OR几乎相似，表明没有相互作用。