DiabetesMellitusandtheRiskofProstateCancerinItaly A. Tavani a, * , S. Gallus a , M. Bertuzzi a , L. Dal Maso b , A. Zucchetto b , E. Negri a , S. Franceschi c , V. Ramazzotti d , M. Montella e , C. La Vecchia a,f a Istituto di Ricerche Farmacologiche ‘‘Mario Negri’’, Via Eritrea 62, 20157 Milan, Italy b Servizio di Epidemiologia e Biostatistica, Centro di Riferimento Oncologico, Aviano (PN), Italy c International Agency for Research on Cancer, Lyon, France d Servizio Integrato di Epidemiologia e Sistemi Informativi, Istituto Regina Elena per lo Studio e la Cura dei Tumori, Rome, Italy e Servizio di Epidemiologia, Istituto Tumori ‘‘Fondazione Pascale’’, Naples, Italy f Istituto di Statistica Medica e Biometria, Universita ` degli Studi di Milano, Milan, Italy Accepted 29 October 2004 Available online 24 November 2004 Abstract Objective: We investigated the relation between diabetes and the risk of prostate cancer, as epidemiological results are controversial. Methods: A hospital-based case-control study was conducted in Italy between 1991 and 2002. Cases were 1294 men, aged <75 years, with incident histologically confirmed prostate cancer, and controls were 1451 men, aged <75 years, admitted to hospital for acute non-neoplastic diseases. Odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated using unconditional multiple logistic regression models. Results: No material association between diabetes and prostate cancer was observed, with a multivariate OR of 1.02 (95%CI 0.75–1.40). Prostate cancer was not related to time since diagnosis of diabetes (OR 0.82 and 0.97 for <5 and 15 years since diagnosis respectively). The OR were respectively 1.63 (95%CI 0.70–3.81) and 0.96 (95%CI 0.68– 1.34) in men diagnosed with diabetes at age <45 or 45 years. The risk estimates were similar across strata of age at interview, body mass index and, among cases, of Gleason score. Conclusions: This study shows no material association between diabetes and prostate cancer risk. # 2004 Elsevier B.V. All rights reserved. Keywords: Prostate cancer; Diabetes mellitus; Risk factors; Case-control studies 1. Introduction The relation between diabetes and prostate cancer risk is complex [1]. Diabetes might reduce the risk of prostate cancer, since men with Type 2 diabetes have lower androgen levels [2], which, in turn, have been directly associated with prostate cancer risk [3]. On the other hand, diabetes is associated with changes in insulin levels and demand, which tend to be higher in pre- and early diabetic stats. These lead to decreased insulin-like growth factor-I (IGF-I), binding protein levels and, consequently, to higher IGF-I, all factors possibly associated with the risk of prostate cancer [4]. However, as diabetes progresses it is characterized by a failure of pancreatic beta-cells to meet insulin demand, and hence by a reduced insulin response. Epidemiological evidence on the possible relation between hyperglycemia and prostate cancer is incon- sistent. A Chinese case-control study [5] found an elevated risk for the highest level of insulin resistance (odds ratio, OR, 2.78). Metabolic syndrome was also related to prostate cancer in a Finnish study [6], but no relation was observed between various measures of insulin resistance in the Northern Sweden Health and Disease Cohort [7] and in the Chicago Heart Associa- tion Detection Project in Industry [8]. Table 1 gives the results of selected studies on the relation between diabetes and prostate cancer. These include at least ten cohort [9–18] and eight case-control European Urology European Urology 47 (2005) 313–317 * Corresponding author. Tel. +39 02 39014.460; Fax: +39 02 39001916. E-mail address: tavani@marionegri.it (A. Tavani). 0302-2838/$ – see front matter # 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2004.10.027