title: Urinary pH, cigarette smoking and bladder cancer risk.
abstract: 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.
authors.affiliation: Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Bethesda, MD 20892, USA. alguacil@dbasp.uhu.es
authors.forename: Juan
authors.initials: J
authors.lastname: Alguacil
authors.forename: Manolis
authors.initials: M
authors.lastname: Kogevinas
authors.forename: Debra T
authors.initials: DT
authors.lastname: Silverman
authors.forename: Núria
authors.initials: N
authors.lastname: Malats
authors.forename: Francisco X
authors.initials: FX
authors.lastname: Real
authors.forename: Montserrat
authors.initials: M
authors.lastname: García-Closas
authors.forename: Adonina
authors.initials: A
authors.lastname: Tardón
authors.forename: Manuel
authors.initials: M
authors.lastname: Rivas
authors.forename: Montserrat
authors.initials: M
authors.lastname: Torà
authors.forename: Reina
authors.initials: R
authors.lastname: García-Closas
authors.forename: Consol
authors.initials: C
authors.lastname: Serra
authors.forename: Alfredo
authors.initials: A
authors.lastname: Carrato
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.forename: Joan
authors.initials: J
authors.lastname: Fortuny
authors.forename: Claudine
authors.initials: C
authors.lastname: Samanic
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000209:etiology* / Q000652:urine*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000209:etiology* / Q000652:urine*; D055815:Young Adult