Abstract
Pancreatic cancer is associated with both family and hereditary cancer syndromes. Multigene panel testing for pancreatic cancer detected the germline variants BRCA1/2, PALB2, ATM, TP53, MLH1, STK11/LKB1, APC, CDKN2A, and SPINK1/PRSS1 as high-risk genes. A latest genome-wide association study revealed the common, but low-risk germline variants in pancreatic cancer patients. Active pancreatic surveillance using magnetic resonance imaging and endoscopic ultrasound is recommended for high-risk individuals who have a family history of pancreatic cancer or harbor these germline pathogenic variants to improve the detection rate and prognosis of pancreatic cancer. Since poly-ADP-ribose polymerase (PARP) inhibitor has been shown to be effective in improving the prognosis of BRCA-positive pancreatic cancer as well as hereditary breast and ovarian cancer syndrome, PARP inhibitor therapy is currently being applied as precision medicine to pancreatic cancer patients harboring the BRCA1/2 germline variant. This review highlights the importance of surveillance for germline pathogenic variants in pancreatic cancer and is expected to lead to improvements in the diagnosis and prevention of pancreatic cancer as well as facilitate the development of effective therapeutic strategies and precision medicine.
Highlights
Pancreatic cancer is a multifactorial genetic disease
There are known germline pathogenic variants associated with hereditary pancreatic cancer, which is closely related to other hereditary tumor syndromes
A National Familial Pancreas Tumor Registry (NFPTR; http://pathology.jhu.edu/pancreas/nfptr/index.php) analysis of the germline DNA of 638 familial pancreatic cancer patients from 593 kindreds revealed that germline pathogenic variants of ATM, BRCA2, Cyclin‐dependent kinase inhibitor 2A (CDKN2A), and PALB2 elevated the risk of pancreatic cancer, and that variants of BUB1B, CPA1, FANCC, and FANCG are detected more frequently in familial than in sporadic pancreatic cancer [37]
Summary
Pancreatic cancer is a multifactorial genetic disease. There are known germline pathogenic variants associated with hereditary pancreatic cancer, which is closely related to other hereditary tumor syndromes. PALB2 pathogenic germline variants are associated with a 7.18, 2.91, and 2.37 RR of developing female breast, ovarian, and pancreatic cancer, respectively, and their estimated incidence up to age 80 years is 53%, 5%, and 2%–3%, respectively [17]. The ATM pathogenic germline variant is strongly associated with breast, ovarian, prostate, and pancreatic cancer.
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