摘要
目的以咖啡因为代谢探针 ,研究膀胱癌发生发展的N_乙酰化代谢表型分布的统计学相关性。方法根据人尿液中咖啡因代谢物5 -乙酰氨基_6_甲酰氨基_3_甲基尿嘧啶(AFMU)和甲磺嘌呤1X)的峰高比值绘制概率分布直方图和概率单位图 ,寻找区分快慢乙酰化代谢表型的截点 ,确定人的乙酰化代谢表型分布。结果健康志愿者和膀胱癌患者概率分布直方图和概率单位图呈明显多态性 ,截点为1 10 ,即大于1.10为快乙酰化代谢表型 ,小于1.10为慢乙酰化代谢表型。健康志愿者中快、慢人乙酰化表型分别为149例(73 7 %)和54例(26 3 %)。膀胱癌患者分别为36例(53 7 %)和31例(46 3) ,两者存在显著统计学差异(P<0.01)。志愿者和膀胱癌患者基因频率分别为0.51和0 68 ,优势比为2 376(95 %可信区间为1 3513和4 1776)。
Aim Acetylator status of 203 healthy controls and 67 patients with bladder cancer was observed .Methods All the subjects were N_acetylate_phenotyped with caffeine as a metabolic probe drug. Urine samples were collected 2 hours after a cup of 140 mg_caffeine_spiked coffee was taken under fasting condition in the morning. The caffeine metabolites, 5_acetylamino_6_formylamino_1_methyluracil (AFMU) and 1_ methylxanthine (1X) were analysed by High Performance Liquid Chromatography (HPLC). The frequence histogram and probit plot were constructed to select the antimode which was used to assess slow and fast acetylator status both in healthy controls and patients with bladder cancer. Results The peak hight ratios (PHR) of AFMU/1X were from 0.06 to 6.5 for healthy voluteers and 0.1 to 6.31 for patients with bladder cancer. Of the 203 healthy controls involved in this study 73.7% (149/203) had the AFMU/1X>1.10, and were classified as fast acetylators, and 26.3% (54/203) as slow acetylators, while 53.7%(36/67) were fast acetylators and 46.3%(31/67) were slow acetylators in patients with bladder cancer.The odds ratio was 2.376, and the gene freqency for healthy controls and for patients with urinary bladder cancer was 0.51 and 0.68 respectively.Conclusion The acetylator status of Chinese population is polymorphic and completely in concordance with that determined by dapsone, isoniazid or sulfamethazine methords as previously reported.Slow acetylators might be susceptible to urinary bladder cancer.
