CCR New

Downloa creatic cancer (PC) is a highly lethal disease with complex etiology involving both environmental netic factors. Although cigarette smoking is known to explain 25% of cases, data from recent studies sugat obesity and long-term type II diabetes are twomajor modifiable risk factors for PC. Furthermore, obed diabetes seem to affect the clinical outcome of patients with PC. Understanding themechanistic effects sity and diabetes on the pancreasmay identify new strategies for prevention or therapy. Experimental and iologic evidence suggests that the antidiabetic drugmetformin has protective antitumor activity in PC. In on to insulin resistance and inflammation as mechanisms of carcinogenesis, obesity and diabetes are to impairments in endothelial function and coagulation status, which increase the risks of thrombosis ngiogenesis and, in turn, the risk of PC development and progression. The associations of the ABO group gene andNR5A2 gene variants with PC discovered by recent genome-wide association studies ink insulin resistance, inflammation, and thrombosis to pancreatic carcinogenesis. These exciting may l findings open new avenues for understanding the etiology of PC and provide opportunities for developing novel strategies for prevention and treatment of this disease. Clin Cancer Res; 16(17); 4313–8. ©2010 AACR.