Genetics and Prevention of Pancreatic Cancer

Abstract

Background: Pancreatic cancer is an aggressive disease with a poor prognosis. Hereditary factors have been reported in up to 10% of cases of pancreatic cancer. The clinical characteristics and genetic abnormalities have been identified for a proportion of this high-risk group, and the development of preventive strategies for these individuals is now a primary goal of cancer clinicians. Methods: A review of the current literature regarding the genetics, screening, and prevention of pancreatic cancer and its precursor lesions was undertaken. Results: Risk factors for pancreatic cancer include smoking, chronic pancreatitis, and a genetic predisposition. The role of diabetes or a diet high in fat or meat remains unclear. The genetic mutations that accompany pancreatic cancer appear to occur in a temporal sequence, beginning in the earliest of precursor lesions. These mutations are detectable in pancreatic juice and, in conjunction with imaging, form the basis of screening programs for high-risk individuals. Not all precursor lesions will undergo malignant transformation, and testing is currently limited in its ability to determine which lesions will undergo transformation. Conclusions: Avoiding tobacco smoking and minimizing risk factors associated with chronic pancreatitis are recommended to reduce the risk of pancreatic cancer. Individuals with a high-risk genetic background require counseling, genetic testing if appropriate (BRCA2 mutation or p16INK4A inactivity) and secondary screening for pancreatic cancer in specialist centers. Risk stratification will improve as more genetic abnormalities causing pancreatic cancer are defined.