Diabetes mellitus and gynecologic cancer: molecular mechanisms, epidemiological, clinical and prognostic perspectives

Diabetes mellitus, the prevalence of which has increased dramatically worldwide, may put patients at a higher risk of cancer. The aim of our study is the clarification of the possible mechanisms linking diabetes mellitus and gynecological cancer and their epidemiological relationship. This is a narrative review of the current literature, following a search on MEDLINE and the Cochrane Library, from their inception until January 2012. Articles investigating gynecologic cancer (endometrial, ovarian, and breast) incidence in diabetic patients were extracted. The strong evidence for a positive association between diabetes mellitus and the risk for cancer indicates that energy intake in excess to energy expenditure, or the sequelae thereof, is involved in gynecological carcinogenesis. This risk may be further heightened by glucose which can directly promote the production of tumor cells by functioning as a source of energy. Insulin resistance accompanied by secondary hyperinsulinemia is hypothezised to have a mitogenic effect. Steroid hormones are in addition potent regulators of the balance between cellular differentiation, proliferation, and apoptosis. Inflammatory pathways may also be implicated, as a correlation seems to exist between diabetes mellitus and breast or endometrial carcinoma pathogenesis, although an analogous correlation with ovarian carcinoma is still under investigation. Antidiabetic agents have been correlated with elevated cancer risk, while metformin seems to lower the risk. Diabetes mellitus is associated with an elevation in gynecologic cancer risk. Moreover, there are many studies exploring the prognosis of patients with diabetes and gynecological cancer, the outcome and the overall survival in well-regulated patients.