The excess of bladder cancer in males (M:F ratio of 4:1 in the United States) is not explained fully by gender differences in smoking habits or occupational exposures. Laboratory studies suggest that some androgenic hormones stimulate (or do not inhibit) oncogenesis in bladder tissue, and that estrogenic hormones have the opposite effect. These observations suggest that bladder cancer risk in females may be modified by sex hormones which undergo profound changes during and following pregnancy. Mail-questionnaire data from 317 incident female cases, and 833 population-based controls in Iowa were used to measure the effect of parity and maternal age at first birth on bladder cancer risk. Parous women were at decreased risk relative to nulliparous women (odds ratio [OR]=0.67, 95 percent confidence interval [CI]=0.44–1.00), after adjustment for age, tobacco use, and previous bladder infection. The overall risk reduction was restricted to women who had never smoked (OR=0.51, CI=0.30–0.88), with no apparent effect of parity among ever-smokers (OR=0.93, CI=0.49–1.77). Risk appeared to decrease with increasing age at first birth, but did not vary with increasing parity after the first birth. Our findings are consistent with the hypothesis that oncogenesis in transitional cell tissue of the human bladder is influenced by sex hormones, and that hormonal changes related to pregnancy thereby can decrease risk.
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References
Muir C, Waterhouse J, Mack T, Powell J, Whelan S. Cancer in Five Continents, Vol. V. Lyon France: International Agency for Research on Cancer, 1987; IARC Sci. Publ. No. 88.
Hartge P, Harvey EB, Linehan WM, et al. Unexplained excess risk of bladder cancer in men. JNCI 1990; 82: 1636–40.
Plesko I, Preston-Martin S, Day NE, Tzonou A, Dimitrova E. Parity and cancer risk in Slovakia. Int J Cancer 1985; 15: 529–33.
Green A, Beral V, Moser K. Mortality in women in relation to their childbearing history. Br Med J 1988; 297: 391–5.
Miller AB, Barclay THC, Choi NW, et al. A study of cancer, parity and age at first pregnancy. J Chron Dis 1980; 33: 595–605.
Kono N, Tanahashi T, Suzawa N, Azuma C. Effects of sex hormones on oncogenesis in rat urinary bladder by N-butyl-N-(4-hydroxybutyl)-nitrosamine. Int J Clin Pharmacol 1977; 15: 101–5.
Reid LM, Leav I, Kwan PWL, Russell P, Merk FB. Characterization of a human, sex steroid-responsive transitional cell carcinoma maintained as a tumor line (R198) in athymic nude mice. Cancer Res 1984; 44: 4560–73.
Burek JD, Hollander CF. Incidence patterns of spontaneous tumors in BN/Bi rats. JNCI 1977; 58: 99–105.
Bertram JS, Craig AW. Specific induction of bladder cancer in mice by butyl-(4-hydroxybutyl)-nitrosamine and the effects of hormonal modifications on the sex difference in response. Eur J Cancer 1972; 8: 587–96.
Cox DR. The Analysis of Binary Data. London: Methuen, 1970: 14.
Dixon WJ, ed. BMDP Statistical Software, Berkeley, CA: University of California Press, 1983: 330.
Gordon GB, Helzlsouer KJ, Comstock GW. Serum levels of dehydroepiandrosterone and its sulfate and the risk of developing bladder cancer. Cancer Res 1991; 51: 1366–9.
Laor E, Tolia BM, Schiffman ZJ, et al. Androgen receptors in bladder tumors. Urology 1985; 25: 161–3.
Weisburger EK, Grantham PH, Weisburger JH. Differences in the metabolism of N-hydroxy-N-2-fluorenyl-acetamide in male and female rats. Biochemistry 1964; 3: 808–12.
Lilienfeld AM, Levin ML, Kessler II. Mortality and marital status. In: Lilienfeld AM, Levin ML, Kessler II, eds. Cancer in the United States. Cambridge, MA: Harvard University Press, 1972: 123–49.
Piper JM. Bladder Cancer in Young Women. Doctoral dissertation, Johns Hopkins University (Baltimore, MD), 1983.
Stanford JL, Hartge P, Brinton LA, Hoover RN, Brookmeyer R. Factors influencing the age at natural menopause. J Chron Dis 1987; 11: 995–1002.
Baron JA. Smoking and estrogen-related disease. Am J Epidemiol 1984; 119: 9–22.
Wald N, Baron J, eds. Smoking and Hormone-Related Disorders. New York: Oxford University Press, 1990.
Kelsey JL, Hildreth NG. Breast and Gynecologic Cancer Epidemiology. Boca Raton, FL: CRC Press, 1983.
Logsden-Sackett N, Lynch CF, Cantor KP, Olson DB, Edwards SL, Johnson DL, VanLier S. Design issues in a large population-based case-control study in Iowa (in preparation, 1992).
Cahill DW, Bashirelahi N, Solomon LW, Dalton T, Salcman M, Ducker TB. Estrogen and progesterone receptors in meningiomas. J Neurosurg 1984; 60: 985–93.
Schnegg J-F, Gomez F, LeMarchand-Beraud T, de Tribolet N. Presence of sex steroid hormone receptors in meningioma tissue. Surg Neurol 1981; 15: 415–18.
Davis FG, Furner SE, Persky V, Koch M. The influence of parity and exogenous female hormones on the risk of colorectal cancer. Int J Cancer 1989; 43: 587–90.
Peters RK, Pike MC, Chang WWL, Mack TM. Reproductive factors and colon cancers. Br J Cancer 1990; 61: 741–8.
La Vecchia C, Franceschi S. Reproductive factors and colorectal cancer. Cancer Causes Control 1991; 2: 193–200.
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Dr Cantor is with the Environmental Epidemiology Branch, National Cancer Institute. Dr Lynch and Ms Johnson are in the Department of Preventive Medicine, University of Iowa School of Medicine, Iowa City, Iowa. Address correspondence to Dr Cantor at NCI, Executive Plaza North, Suite 443, Bethesda, MD 20892, USA. This research was supported in part by National Cancer Institute research contracts NCI-NO1-CP-51026 and NCI-NO1-CP-85614, and by a Public Health Service Preventive Oncology Academic Award, 5 KO7 CA01181-04.
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Cantor, K.P., Lynch, C.F. & Johnson, D. Bladder cancer, parity, and age at first birth. Cancer Causes Control 3, 57–62 (1992). https://doi.org/10.1007/BF00051913
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DOI: https://doi.org/10.1007/BF00051913