Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Bethesda, MD 20892, USA.
Carcinogenesis. 2011 Jun;32(6):843-7. doi: 10.1093/carcin/bgr048. Epub 2011 Mar 14.
Glucuronide conjugates of 4-aminobiphenyl and its N-hydroxy metabolite can be rapidly hydrolyzed in acidic urine to undergo further metabolic activation and form DNA adducts in the urothelium. We conducted a large multicenter case-control study in Spain to explore the etiology of bladder cancer and evaluated the association between urine pH and bladder cancer risk, alone and in combination with cigarette smoking. In total, 712 incident urothelial cell carcinoma cases and 611 hospital controls directly measured their urine pH with dipsticks twice a day (first void in the morning and early in the evening) during four consecutive days 2 weeks after hospital discharge. We found that a consistently acidic urine pH ≤6.0 was associated with an increased risk of bladder cancer [odds ratio (OR) = 1.5, 95% confidence interval (CI): 1.2-1.9] compared with all other subjects. Furthermore, risk estimates for smoking intensity and risk of bladder cancer among current smokers tended to be higher for those with a consistently acidic urine (OR = 8.8, 11.5 and 23.8) compared with those without (OR = 4.3, 7.7 and 5.8, respectively, for 1-19, 20-29 and 30+ cigarettes per day; P(interaction) for 30+ cigarettes per day = 0.024). These results suggest that urine pH, which is determined primarily by diet and body surface area, may be an important modifier of smoking and risk of bladder cancer.
4-氨基联苯及其 N-羟化物的葡糖苷酸缀合物可以在酸性尿液中迅速水解，从而进一步代谢激活，并在尿路上皮中形成 DNA 加合物。我们在西班牙进行了一项大型多中心病例对照研究，以探讨膀胱癌的病因，并评估尿液 pH 值与膀胱癌风险的关联，单独评估以及与吸烟联合评估。共有 712 例初发的尿路上皮细胞癌病例和 611 例医院对照者在出院后 2 周内，每天用尿试纸两次（早上第一次和傍晚第一次）连续 4 天直接测量尿液 pH 值。我们发现，与所有其他受试者相比，持续酸性尿液 pH 值≤6.0 与膀胱癌风险增加相关[比值比（OR）=1.5，95%置信区间（CI）：1.2-1.9]。此外，对于当前吸烟者，吸烟强度和膀胱癌风险之间的风险估计值在持续酸性尿液者中（OR=8.8、11.5 和 23.8）比在非酸性尿液者中（OR=4.3、7.7 和 5.8，分别对应于每天 1-19、20-29 和 30+ 支香烟；每天 30+ 支香烟的 P（交互作用）=0.024）更高。这些结果表明，尿液 pH 值主要由饮食和体表面积决定，可能是吸烟和膀胱癌风险的重要修饰因子。
