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Genetic susceptibility to pancreatic cancer.
Pancreatic cancer is the fourth leading cause of cancer death in both men and women in the United States. However, it has the poorest prognosis of any major tumor type, with a 5-yr survival rate of approximately 5%. Cigarette smoking, increased body mass index, heavy alcohol consumption, and a diagnosis of diabetes mellitus have all been demonstrated to increase risk of pancreatic cancer. A family history of pancreatic cancer has also been associated with increased risk suggesting inherited genetic factors also play an important role, with approximately 5-10% of pancreatic cancer patients reporting family history of pancreatic cancer. While the genetic basis for the majority of the familial clustering of pancreatic cancer remains unclear, several important pancreatic cancer genes have been identified. These consist of high penetrance genes including BRCA2 or PALB2, to more common genetic variation associated with a modest increase risk of pancreatic cancer such as genetic variation at the ABO blood group locus. Recent advances in genotyping and genetic sequencing have accelerated the rate at which novel pancreatic cancer susceptibility genes have been identified with several genes identified within the past few years. This review addresses our current understanding of the familial aggregation of pancreatic cancer, established pancreatic cancer susceptablity genes and how this knowledge informs risk assessment and screening for high-risk families.
Department of Oncology and Pathology, Sol Goldman Pancreatic Cancer Research Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
MeSHColorectal Neoplasms, Hereditary Nonpolyposis
Early Detection of Cancer
Genetic Predisposition to Disease
Tumor Suppressor Proteins
Pub Type(s)Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't