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Pancreatic cancer 1

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Carcinoma of pancreas

Pancreatic cancer shows among the highest mortality rates of any cancer, with a 5-year relative survival rate of less than 5%. By the time of initial diagnosis, metastatic disease is commonly present. Established risk factors include a family history of pancreatic cancer, a medical history of diabetes type 2, and cigarette smoking (summary by Amundadottir et al., 2009). Genetic Heterogeneity of Pancreatic Cancer Somatic mutations in pancreatic cancer occur in the KRAS (190070), CDKN2A (600160), MADH4 (600993), TP53 (191170), ARMET (601916), STK11 (602216), ACVR1B (601300), and RBBP8 (604124) genes. Susceptibility loci for pancreatic cancer include PNCA1 (606856), related to mutation in the PALLD gene on chromosome 4q32 (608092); PNCA2 (613347), related to mutation in the BRCA2 gene on chromosome 13q12 (600185); PNCA3 (613348), related to mutation in the PALB2 gene on chromosome 16p12 (610355); and PNCA4 (614320), related to mutation in the BRCA1 gene on chromosome 17q21 (113705). Occurrence of Pancreatic Cancer in Other Disorders Several familial cancer syndromes increase the risk of pancreatic cancer. The best characterized include hereditary nonpolyposis colon cancer syndrome (HNPCC; see 120435); hereditary breast-ovarian cancer syndrome due to mutations in BRCA2; Peutz-Jeghers syndrome (175200); the melanoma-pancreatic cancer syndrome (606719), caused by mutations in CDKN2A (600160); von Hippel-Lindau syndrome (193300), ataxia-telangiectasia (208900) (Swift et al., 1976), and juvenile polyposis syndrome (174900). Patients with hereditary pancreatitis (167800) resulting from gain-of-function mutations in the protease serine-1 gene (PRSS1; 276000) have a lifetime pancreatic cancer risk ratio of 57 and a cumulative incidence, to age 70 years, of 40% (Lowenfels et al., 1997). [from OMIM]

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Neoplastic Process

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