Use of prescription diuretics and incidence of renal cell cancer have increased in the United States in the past 25 years. Recent interview-based epidemiologic studies have reported an association between diuretic use and renal cell cancer risk. Our study evaluated this hypothesis using, for the first time, medical records as the source of the information on prescription diuretic use. Using medical records of women from a prepaid health plan, we identified 191 cases and 191 controls matched on age, membership duration, and membership at diagnosis. Diuretics use and history of potential confounding factors were ascertained by a standardized review of the medical records of each subject, without reference to case or control status. There was a strong and statistically significant association between renal cell cancer and prescription diuretics (odds ratio [OR] adjusted for hypertension, smoking, and obesity = 2.9, 95 percent confidence interval [CI]=1.7–4.7). Risk tended to increase with dose, measured by number of prescriptions. Since renal cancer can induce hypertension, which is treated by diuretics, and thereby confound the association with diuretics, we examined diuretic use 10 or more years prior to diagnosis when secondary hypertension would be unlikely. The OR for prescriptions 10 or more years before diagnosis was 3.5 (CI=1.7–7.4). Our results support earlier reports of an excess risk of renal cell cancer among users of prescription diuretics and indicate need for further study to evaluate this relationship, especially due to the extensive use of diuretics and the increasing incidence of this cancer.
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References
Yu MC, Mack TM, Hanish R, Cicioni C, Henderson BE. Cigarette smoking, obesity, diuretic use, and coffee consumption as risk factors for renal cell carcinoma. JNCI 1986; 77: 351–6.
McLaughlin JK, Blot WJ, Fraumeni JFJr. Diuretics and renal cell cancer. JNCI 1988; 80: 378.
Fraser GE, Phillips RL, Beeson WL. Hypertension, antihypertension medication and risk of renal carcinoma in California Seventh-Day Adventists. Int J Epidemiol 1990; 19: 832–8.
Grove JS, Nomura A, Severson RK, Stemmerman GN. The association of blood pressure with cancer incidence in a prospective study. Am J Epidemiol 1991; 134: 942–7.
Mellemgaard A, Moeller H, Olsen JH. Diuretics may increase risk of renal cell carcinoma. Cancer Causes Control 1992; 3: 309–12.
Kreiger N, Marrett LD, Dodds L, Hilditch S, Darlington GA. Risk factors for renal cell carcinoma: Results of a population-based case-control study. Cancer Causes Control 1993; 4: 101–10.
Baum C, Kennedy DL, Knepp DE, Jurgens JP, Faich GA. Prescription drug use in 1984 and changes over time. Med Care 1988; 26: 105–14.
Koch H, Knopp DA. Highlights of drug utilization in office practice: National ambulatory medical care survey, 1985. Adv Data Vital Health Stat 1987; No. 134.
Devesa SS, Silverman DT, McLaughlin JK, Brown CC, Connelly RR, Fraumeni JFJr. Comparison of the descriptive epidemiology of urinary tract cancers. Cancer Causes Control 1990; 1: 133–41.
World Health Organization. International Classification of Disease, Ninth Revision. Geneva: WHO, 1977.
Breslow NE, Day NE. Statistical Methods in Cancer Research Vol. I. Case-control Studies. Lyon, France: International Agency for Research on Cancer, 1980; IARC Sci. Pub. No. 32.
Selby JV, Friedman G, Fireman BH. Screening prescription drugs for possible carcinogenicity: Eleven to fifteen years of follow-up. Cancer Res 1989; 49: 5736–47.
McCredie M, Stewart JH. Risk factors for kidney cancer in New South Wales, Australia. II. Urologic diseases, hypertension, and hormonal factors. Cancer Causes Control 1992; 3: 323–31.
McLaughlin JK, Blot WJ, Devesa SS, Fraumeni JF Jr. Renal cancer. In: Schottenfeld D, Fraumeni JF Jr, eds. Cancer Epidemiology and Prevention. New York: Oxford University Press (in press).
Laski ME. Diuretics: Mechanism of action and therapy. Sem Nephrol 1986; 6: 210–33.
Bennington JL, Beckwith JB. Atlas of Tumor Pathology. Tumors of the Kidney, Renal Pelvis, and Ureter. Bethesda, Maryland: Armed Forces Institute of Pathology, 1975: 93–199.
Lijinsky W, Reuber MD. Pathologic effects of chronic administration of hydrochlorothiazide, with and without sodium nitrate, to F344 rats. Tox Ind Health 1987; 3: 413–22.
National Toxicology Program. Toxicology and Carcinogenesis Studies of Hydrochlorothiazide in F344/N Rats and B6C3F Mice (Feed Studies). Technical Report Series 357. Washington, DC: USHHS, PHS, NIH, 1989; NIH Pub. No. 89–2812.
National Toxicology Program. Toxicology and Carcinogenesis Studies of Furosemide in F344/N Rats and B6C3F Mice (Feed Studies). Technical Report Series 356. Washington, DC: USHHS, PHS, NIH, 1989; NIH Pub. No. 89–2811.
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Drs Finkle, Rasgon, Yeob, and Low are with the Southern California Permanente Medical Group, Pasadena, CA, USA. Dr McLaughlin is with the Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer Institute, Bethesda, MD, USA. Address correspondence to Dr Finkle, Department of Research and Evaluation, Southern California Permanente Medical Group, 100 S. Los Robles Avenue, Second Floor, Pasadena, CA 91101, USA. This research was sponsored by NIH contract NO1 CP 95680.
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Finkle, W.D., McLaughlin, J.K., Rasgon, S.A. et al. Increased risk of renal cell cancer among women using diuretics in the United States. Cancer Causes Control 4, 555–558 (1993). https://doi.org/10.1007/BF00052431
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DOI: https://doi.org/10.1007/BF00052431