Abstract 3620: Diabetes mellitus and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition.
Authors: Tsilidis Konstantinos K. , Allen Naomi , Travis Ruth , Rohrmann Sabine , Nöthlings Ute , Arriola Larraitz , Gunter Marc , Key Timothy 
Published: August 2014

Abstract
The current epidemiologic evidence suggests that men with type 2 diabetes mellitus may be at lower risk of developing prostate cancer. More research is needed to clarify whether and how time since diabetes diagnosis, diabetes treatment, stage and grade of prostate cancer, age at recruitment, adiposity, and physical activity modify the risk profile. We assessed the association of self-reported history of diabetes mellitus diagnosis at baseline with risk of prostate cancer among 139,131 men recruited into the European Prospective Investigation into Cancer and Nutrition (EPIC), after excluding men with prevalent cancer at recruitment and men who did not return the baseline questionnaires or had missing information about their history of diabetes. After an average of 12 years follow-up, 4,531 prostate cancers were diagnosed, of which 894 men had advanced (T3-4, N+, M+) disease and 1,688 had localized disease (T0-2, N0, M0); 375 men had high-grade disease (Gleason score ≥ 8) disease and 1,811 had low-grade disease (Gleason score &lt; 8). Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards models stratified by EPIC recruitment center and age at enrolment, and adjusted for body mass index, waist circumference, cigarette smoking status, university education, physical activity, and daily dietary intake of energy, alcohol, fruits and vegetables, fish, calcium and protein from dairy sources. A total of 5,100 men (3.7%) stated at baseline that they had a history of diabetes mellitus. Men with diabetes had a 26% reduced risk of developing prostate cancer compared to men without diabetes (HR, 0.74; 95% CI, 0.63-0.86). There was no significant reduction in risk in the first two years after diabetes diagnosis (No. of cases, 39; HR, 0.83; 95% CI, 0.60-1.14), but was evident for men diagnosed between 3 to 6 years after diagnosis (No. of cases, 32; HR, 0.72; 95% CI, 0.51-1.02) and 7-12 years (No. of cases, 32; HR, 0.75; 95% CI, 0.53-1.07), and was even lower for men who had been diagnosed for more than 12 years (No. of cases, 31; HR, 0.64; 95% CI, 0.45-0.92). Compared to non-diabetics, diabetic men not receiving insulin treatment at baseline had a risk of prostate cancer (HR, 0.75; 95% CI, 0.60-0.94) similar to what of diabetic men who were receiving insulin (HR, 0.78; 95% CI, 0.59-1.03). These results did not differ by stage and grade of prostate cancer, or by age at recruitment, adiposity, or physical activity. Our results are compatible with the hypothesis that diabetes is associated with reduced prostate cancer risk. A potential biological explanation underlying this association is that men with severe type 2 diabetes may manifest lower testosterone concentrations, which provide an environment that is not conducive to proliferation of prostate cancer cells.
Citation Format: Konstantinos K. Tsilidis, Naomi Allen, Ruth Travis, Sabine Rohrmann, Ute Nöthlings, Larraitz Arriola, Marc Gunter, Timothy Key. Diabetes mellitus and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3620. doi:10.1158/1538-7445.AM2013-3620