Cigarette Smoke and Pancreatic Carcinogenesis

Pancreatic cancer is the 4th leading cause of death from cancer. It is estimated that about 37,680 people will develop pancreatic cancer and that 34,290 will die from it in 2008. The five-year survival rate for pancreatic cancer is only 5%, making it one of the deadliest forms of cancer. A number of risk factors have been established for pancreatic cancer, but the most established environmental risk factor is cigarette smoking. It is estimated that tobacco smoking increases the risk of pancreatic cancer by at least 2- to 3- fold. However, the molecular mechanisms by which cigarette smoke contributes to pancreatic cancer are largely unknown. Recently, a mouse model of experimental pancreatic carcinogenesis has been developed. This model closely resembles human pancreatic cancer. In this application, we propose to test the hypothesis that exposure to cigarette smoke accelerates pancreatic carcinogenesis in this mouse model. Mice will be exposed to cigarette smoke or ambient air (for controls) for 5 or 9 months and the development of pancreatic tumors and precancerous lesions in the pancreas will be determined. Mechanisms by which cigarette smoke may increase the development of cancer will also be studied. With these studies, we hope to establish an animal model of cigarette smoke-enhanced pancreatic cancer, which can then be sued to examine the natural history of the disease under controlled conditiions, as well as nutritional or other interventions that may protect against the development of pancreatic cancer.