CancerCauses and Control, 1996, 7, pp. 475-478 SHORT REPORT Is diabetes mellitus a risk factor for ovarian cancer? A case-control study in Utah and Washington (United States) Amanda I. Adler, Noel S. Weiss, Mary L. Kamb, and Joseph L. Lyon (Received 13 October 1995;acceptedin revisedform 20 February 1996) Insulin resistance characterizes non-insulln 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 nonepithdial 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. Cancer Causesand Control, 1996, 7, 475-478 Key words: Case-control studies, diabetes mellitus, insulin resistance, ovarian neoplasms. Introduction Generalized insulin resistance, and its compensatory hyperinsulinemia, characterize non-insulin-dependent diabetes mellitus (NIDDM)) Despite systemic insulin- resistance, hyperinsulinemia appears to stimulate ovarian steroid production, probably via insulin receptors found in ovarian stroma, thecal cells, and granulosa cells,v~ Ovarian follicular insulin levels correlate with progesterone levels,5and insulin added to swine granulosa cells stimu- lates progesterone production? Insulin stimulates conversion of testosterone to estradiol in human ovarian cells? In neoplastic tissue, insulin increased androstendione production within an arrhenoblastoma, s Dr Adler is with the Veteran's Administration Hospital, Seattle, WA, USA, and, along with Dr Weiss,with the Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA, and the Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Dr Kamb is with the Centers for Disease Control and Prevention, Division of HIV/AIDS Prevention, Atlanta, GA, USA. Dr Lyon is with the Department of Family and Preventive Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA. Address correspondence to Dr Adler, Department of Healtb Services, Research, and Development, Veterans Administration Hospital, 1660 S. Columbia Way (152), Seattle, WA 98108, USA. This research was supported in part by grants R35-CA-39779 and 2T32-CA-09168 from the US National Cancer Institute. ~) 1996 Rapid Science Publishers Cancer Causes aad Control Vol 7. 19% 475