Prevention of Pancreatic Cancer and Strategies for Management of Familial Pancreatic CancerHruban R.H. · Canto M.I. · Yeo C.J.
At the current time, pancreatic cancer remains a difficult and typically fatal disease. A number of case reports and case-control epidemiologic studies have suggested that familial aggregation plays a role in as many as 10% of all pancreatic cancers. During the last several years, genetic alterations responsible for syndromes linked with pancreatic cancer have been identified. These genes include BRCA2, p16, PRSS1, STK11, and various mismatch repair genes. Unfortunately, most kindreds with a familial aggregation cannot be explained by one of these known genetic syndromes. Recent data from the National Familial Pancreas Tumor Registry at Johns Hopkins have estimated the prospective risk of pancreatic cancer among first-degree relatives of pancreatic cancer patients. The risk was estimated by comparing observed new cases of pancreatic cancer to expected numbers. In families where three first-degree relatives had been diagnosed with pancreatic cancer, the risk of another individual developing pancreatic cancer rose to a 57-fold increase over the basal risk. This article reviews the data concerning familial pancreatic cancer. Additionally, this article reviews the data concerning the histological precursors of invasive ductal adenocarcinoma of the pancreas: pancreatic intraepithelial neoplasias. Further, the current Johns Hopkins methodology used to screen for early pancreatic neoplasia in familial pancreatic cancer patients and in patients with familial Peutz-Jeghers syndrome is discussed. In summary, the notable advances in the field of molecular genetics have allowed for a better definition of the genetics of pancreatic cancer. With this knowledge has evolved a better understanding of several high-risk clinical syndromes associated with pancreatic cancer, familial pancreatic cancer, and the evolution of strategies to screen high-risk families for early pancreatic neoplasia.
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