Kaye M. Reid Lombardo, M.D.

Pancreatic cancer, a lethal malignancy, afflicts over 33,000 annually in the United States. Though much investigation is underway to clarify the biology and natural history of this disease, even basic questions, such as etiology, remain unknown. There is, however, more than suggestive evidence in the literature of a link between chronic inflammation and progression to pancreatic cancer. Current thinking is that this progression is mediated by proinflammatory mediators such as cyclooxygenase (COX) and nitric oxide (NO). These substances are found to be upregulated in pancreatic cancer tissue but not in normal adjacent tissue. We postulate that the association between inflammation and pancreatic adenocarcinoma is also facilitated by host susceptibility, specifically by genetic polymorphisms of inflammation-related genes.

My long term goal is to advance the understanding of how inflammatory processes lead to the development of pancreatic cancer. The objective of this KL2 proposal is to identify potential disease-susceptibility genes, focusing on inflammation-related genes, in patients with pancreatic ductal adenocarcinoma compared to healthy controls. We also want to determine how polymorphisms of inflammation-related genes interact with environmental factors, namely, smoking and nonsteroidal anti-inflammatory drugs (NSAIDs). In addition we will examine how the presence of polymorphisms in pancreatic cancer patients affects their survival after surgical resection. The motivation for this proposed study is to identify a cause of pancreatic cancer in which a biomarker for risk or target for chemoprevention can be elucidated in order to decrease the impact of this very morbid and lethal disease. This project is feasible principally because of the experience and expertise of the multidisciplinary team that has been assembled to support and complete this project.