Genetic predisposition to bladder cancer: ability to hydroxylate debrisoquine and mephenytoin as risk factors.
Genetic predisposition to bladder cancer: ability to hydroxylate debrisoquine and mephenytoin as risk factors.
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发表时间：
1987-10
期刊：
影响因子：
11.2
通讯作者：
A. Kaisary;P. Smith;Evelyne Jaczq;C. Mcallister;G. Wilkinson;W. Ray;R. Branch
中科院分区：
文献类型：
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作者：
A. Kaisary;P. Smith;Evelyne Jaczq;C. Mcallister;G. Wilkinson;W. Ray;R. Branch
假设的氧化药物代谢活性的指标的频率分布是不同的膀胱癌患者（n = 98）和年龄，性别匹配的对照组（n = 110）进行了研究。在同时给予异喹胍（10 mg）和外消旋美芬妥英（100 mg）后8小时尿样中测定了异喹胍的尿回收率和美芬妥英的R/S比。此外，酒精消费，吸烟习惯，乙酰化表型（使用100毫克氨苯砜作为底物）已被测量。膀胱癌患者根据组织学标准分为侵袭性（III期）（34%）或非侵袭性（I期和II期）（66%）疾病。侵袭性膀胱癌患者的异喹胍尿回收率的频率分布中位数大于对照组，只有4例患者的回收率低于对照组的平均值。使用逻辑回归分析，有效的异喹代谢和吸烟和饮酒之间的协同作用是显着的，独立的危险因素，而S-美芬妥英羟基化和乙酰化表型不是显着的危险因素。相比之下，非侵袭性膀胱癌患者与S-美芬妥英的快速羟基化有显著但较弱的相关性，这与吸烟和饮酒之间的显著协同作用无关。乙酰化表型和异喹胍尿回收率与非侵袭性癌症风险增加无关。这些结果是一致的概念，氧化同工酶可能是负责转换的环境因素，以接近膀胱癌的非工业相关的膀胱癌。他们还表明，不同的病因因素参与了侵袭性和非侵袭性膀胱癌的发病机制。
The hypothesis that the frequency distribution of indices of oxidative drug-metabolizing activity is different between patients with bladder cancer (n = 98) and age, sex-matched control subjects (n = 110) has been investigated. Urinary recovery ratios of debrisoquine and R/S ratios of mephenytoin have been measured in an 8-h urine sample after simultaneous administration of debrisoquine (10 mg) and racemic mephenytoin (100 mg). In addition, alcohol consumption, smoking habit, and acetylation phenotype (using 100 mg dapsone as a substrate) have been measured. Patients with bladder cancer were classified on histological criteria as having aggressive (Stage III) (34%) or nonaggressive (Stages I and II) (66%) disease. The median of the frequency distribution of the debrisoquine urinary recovery ratio in patients with aggressive bladder cancer was greater than in control subjects, and only four patients had recovery ratios lower than the mean of the control group. Using logistic regression analysis, efficient debrisoquine metabolism and a synergistic interaction between smoking and ethanol consumption were significant, independent risk factors, while S-mephenytoin hydroxylation and acetylation phenotype were not significant risk factors. In contrast, patients with non-aggressive bladder cancer had a significant, but weaker, association with rapid hydroxylation of S-mephenytoin, which was independent of a significant synergistic interaction between smoking and alcohol consumption. Acetylation phenotype and debrisoquine urinary recovery ratio were not associated with increased risk of nonaggressive cancer. These results are consistent with the concept that oxidative isozymes might be responsible for conversion of environmental agents to proximate bladder carcinogens in nonindustrial-related bladder cancer. They also suggest that different etiological factors are involved in the pathogenesis of aggressive and nonaggressive bladder cancer.