Insulin resistance characterizes non-insulin dependent diabetes (NIDDM). Insulin resistance may coexist in clinical syndromes with hyperestrogenism and hyperandrogenism, suggesting that the ovary may be sensitive to effects of insulin. In addition, insulin-like growth factor-I receptors, which are capable of binding insulin, have been identified in ovarian cancer tissue and are proposed to regulate cell growth. We evaluated the association between a history of diabetes mellitus and ovarian cancer in a case-control study in seven counties in Washington and in Utah (United States) during the years 1975–87. Cases included women newly diagnosed with ovarian cancer over a five-year period who were identified through population-based cancer reporting. Controls similar to cases with regard to age and county of residence were identified via household surveys or random digit dialing. The study included 595 cases and 1,587 controls. Twenty-seven cases (4.5 percent) and 72 controls (4.5 percent) reported a history of diabetes. Logistic regression analysis of the association between diabetes and ovarian cancer controlling for age, body mass index, and race resulted in an odds ratio (OR) of 0.9 (95 percent confidence interval [CI]=0.6–1.5). The OR was not changed with further controlling for prior oral contraceptive use or prior pregnancy. None of the 20 women with nonepithelial tumors (15 of which were stromal tumors) had a history of diabetes (upper CI=4.0). These results, together with findings of two earlier cohort studies, do not support the hypothesis that diabetes is a risk factor for epithelial ovarian cancer.
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Reaven GM. Banting Lecture 1988: Role of insulin resistance in human disease. Diabetes 1988; 37: 1595–607.
Poretsky L, Grigorescu F, Seibel M, Moses AC, Flier JS. Distribution and characterization of insulin and insulin-like growth factor I receptors in normal human ovary. J Clin Endocrinol Metal 1985; 61: 728–34.
Poretsky L, Kalin MF. The gonadotropic function of insulin. Endocr Rev 1987; 8: 132–41.
Barbieri RL, Makris AM, Randall RW, Daniels G, Kistner RW, Ryan KJ. Insulin stimulates androgen accumulation in incubations of ovarian stroma obtained from women with hyperandrogenism. J Clin Endocrinol Metab 1986; 62: 904–10.
Diamond MP, Webster BW, Carr RK, Wentz AC, Osteen KG. Human follicular fluid insulin concentrations. J Clin Endocrinol Metab 1985; 61: 990–2.
Veldhuis JD, Kolp LA, Toaff ME, Strauss JF, Demers LM. Mechanisms subserving the trophic actions of insulin on ovarian cells. J Clin Invest 1983; 72: 1046–57.
Garzo VG, Dorrington JH. Aromatase activity in human granulosa cells during follicular development and the modulation by follicle-stimulating hormone and insulin. Am J Obstet Gynecol 1984; 148: 657–62.
Nagamani M, Stuart CA, VanDinh T. Steroid biosynthesis in the Sertoli-Leydig cell tumor: Effects of insulin and luteinizing hormone. Am J Obstet Gynecol 1989; 161: 1738–43.
Chang JR, Nakamura RM, Judd HL, Kaplan SA. Insulin resistance in nonobese patients with polycystic ovarian disease. J Clin Endocrinol Metab 1983; 57: 356–9.
Barbieri RL, Hornstein MD. Hyperinsulinemia and ovarian hyperandrogenism. Endo Metab Clin North America 1988; 17: 685–703.
Barbieri RL, Makris A, Ryan KJ. Insulin stimulates androgen accumulation in incubations of human ovarian stroma and theca. Obstet Gynecol 1984; 64: 73S-80S.
Langford KS, Miell JP. The insulin-like growth factor-1/binding protein axis: physiology, pathophysiology and therapeutic manipulation. Eur J Clinical Invest 1993; 23: 503–16.
LeRoith D. Insulin-like growth factors in health and disease. Ann Intern Med 1992; 116: 854–62.
Foekens JA, VanPutten WLJ, Portengen H, et al. Prognostic value of pS2 protein and receptors for epidermal growth factor (EGF-R), insulin-like growth factor-1 (IGF-1-R) and somatostatin (SS-R) in patients with breast and ovarian cancer. J Steroid Biochem Molec Biol 1990; 37: 815–21.
Resnicoff M, Ambrose D, Coppola D, Rubin R. Insulin-like growth factor-I and its receptor mediate the autocrine proliferation of human-ovarian carcinoma cell lines. Laboratory Invest 1993; 69 (6): 756–60.
Bergh C, Carlsson B, Olsson J-H, Selleskog U, Hillensjo T. Regulation of androgen production in cultured human thecal cells by insulin-like growth factor 1 and insulin. Fertil Steril 1993; 59: 323–31.
Adashi EY, Resnick CE, D'Ercole AJ, Svoboda ME, VanWyk JJ. Insulin-like growth factors as intraovarian regulators of granulosa cell growth and function. Endocr Reviews 1985; 6: 400–20.
Wimalasena J, Meehan D, Dostal R, Foster JS, Cameron M, Smith M. Growth factors interact with estradiol and gonadotropins in the regulation of ovarian cancer cell growth and growth factor receptors. Oncology Research 1993; 5: 325–37.
Moller DE, Flier JS. Insulin resistance—Mechanisms, syndromes, and implications. N Engl J Med 1991; 325: 938–48.
Yee D, Morales FR, Hamilton TC, VonHoff DD. Expression of insulin-like growth factor I, its binding proteins, and its receptor in ovarian cancer. Cancer Res 1991; 51: 5107–12.
Karasik A, Menczer H, Pariente C, Kanety H. Insulin-like growth factor-I (IGF-I) and IGF-binding protein-2 are increased in cyst fluids of epithelial ovarian cancer. J Clin Endo Metab 1994; 78: 271–6.
Kuhnel R, DeGraaff J, Rao BR, Stolk JG. Androgen receptor predominance in human ovarian carcinoma. J Steroid Biochem 1987; 26:393–7.
Rao RB, Slotman BJ. Action and counter-action of hormones in human ovarian cancer. Anticancer Res 1989; 9:1005–8.
Nash JD, Ozols RF, Smyth JF, Hamilton TC. Estrogen and anti-estrogen effects on the growth of human epithelial ovarian cancer in vitro. Obstet Gynecol 1989; 73: 1009–16.
Langdon SP, Hawkes MM, Lawrie SS, et al. Oestrogen receptor expression and the effects of oestrogen and tamoxifen on the growth of human ovarian carcinoma cell lines. Brit J Cancer 1990; 62: 213–6.
Weiss NS, Lyon JL, Liff JM, Vollmer WM, Daling JR. Incidence of ovarian cancer in relation to the use of oral contraceptives. Int J Cancer 1981; 28: 669–71.
Weiss NS, Lyon JL, Krishnamurthy S, Dietert SE, Liff JM, Daling JR. Non-contraceptive estrogen use and the occurrence of ovarian cancer. JNCI 1982; 68: 95–8.
SAS Institute, Inc. SAS User's Guide. Cary, NC (USA): SAS Institute, Inc., 1990.
Nie NH, Hull CH, Jenkins JG, Steinbrenner K, Brent DH. Statistical Package for the Social Sciences (SPSS), Second Edition. New York, NY (USA): McGraw Hill, 1975.
Statistics and Epidemiology Research Corporation. EGRET Software Package. Beattle, WA (USA): SERC, 1990.
Adami H, McLaughlin J, Ekborn A, et al. Cancer risk in patients with diabetes mellitus. Cancer Causes Control 1991; 2: 307–14.
Ragozzino M, Melton LJ, Chu-Pin C, Palumbo PJ. Subsequent cancer risk in the incidence cohort of Rochester, Minnesota, residents with diabetes mellirus. J Chron Dis 1982; 35: 13–9.
Farrow D, Weiss N, Lyon JL, Daling J. Association of obesity and ovarian cancer in a case-control study. Am J Epidemiol 1989; 129: 1300–4.
This research was supported in part by grants R35-CA-39779 and 2T32-CA-09168 from the US National Cancer Institute.
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Adler, A.I., Weiss, N.S., Kamb, M.L. et al. Is diabetes mellitus a risk factor for ovarian cancer? A case-control study in Utah and Washington (United States). Cancer Causes Control 7, 475–478 (1996). https://doi.org/10.1007/BF00052674