Cadmium, K-ras, and Pancreatic Cancer in Egypt

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DESCRIPTION (provided by applicant): Pancreatic cancer is a lethal disease that quickly deprives patients of both quality and quantity of life. It is the fifth leading cause of cancer death in the United States. In 2001, an estimated 29,200 new cases were diagnosed, and 28,900 people died from the disease. The median survival of pancreatic cancer is six months and only 4% of patients are alive five years after diagnosis. Given its incidence and almost entire fatality, substantially increased research efforts are clearly warranted to understand, prevent, and control this disease. Although pancreatic cancer is rare in developing countries, including most of Egypt, the northeast Nile Delta region of Egypt offers a unique setting for studying pancreatic cancer because of: 1) its large number of pancreatic cancer cases; 2) the high serum cadmium levels in residents of the region; and 3) the unique molecular pathologic features of pancreatic cancer tumors of patients from this region [unusually high rate of GGT --> GTT (glycine --> valine) K-ras mutation]. Cadmium has been suspected as a carcinogen for pancreatic cancer and the large number of cases and early-onset disease in addition to the unique K-ras mutations of tumors in this population may be caused by high cadmium exposures. We propose a pilot study to generate a hypothesis that pancreatic cancer, in this population, is caused by high levels of exposure to environmental cadmium. We will recruit 150 pancreatic cancer controls and 150 age-, sex- and residence-matched hospital controls. We will examine lifetime epidemiologic, environmental and cancer family histories to identify novel environmental or lifestyle-related factors that predict risk for pancreatic cancer in this population with high adverse environmental exposures. We will also test serum cadmium levels in cases and controls and K-ras mutation types in tumors of cases to define if the unique mutation types are associated with higher serum cadmium levels or other environmental exposures. This study may define the role of cadmium in the etiology of pancreatic cancer and may set the stage for future studies on gene-environmental interactions in the epidemiology of pancreatic cancer.