Werner syndrome as a hereditary risk factor for exocrine pancreatic cancer: potential role of WRN in pancreatic tumorigenesis and patient-tailored therapy.

Cancer Biology & Therapy
Stephen G Chun, Nelson S Yee

Abstract

Advanced age is considered a risk factor for pancreatic cancer, but this relationship at the molecular and genetic level remains unclear. We present a clinical case series focusing on an association between pancreatic adenocarcinoma and Werner syndrome (WS) that is an autosomal recessive genetic disorder characterized by accelerated aging and cancer predisposition, and is caused by loss-of-function mutations in the WS RecQ helicase gene (WRN). Although pancreatic adenocarcinoma mostly occurs in a sporadic fashion, a minority of cases occurs in the context of susceptible individuals with hereditary syndromes. While WS has not been previously recognized as a risk factor for developing malignant tumors of the exocrine pancreas, the clinicopathologic features of three reported patients suggest a contributory role of WRN deficiency in pancreatic carcinogenesis. Molecular genetic analyses support the role of WRN as a tumor suppressor gene, although recent evidence reveals that WRN can alternatively promote oncogenicity depending on the molecular context. Based upon the clinico-pathologic features of these patients and the role of WRN in experimental models, we propose that its loss-of-function predisposes the development of pancreati...Continue Reading

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Citations

Mar 10, 2016·Oncotarget·Raghavendra A ShamannaVilhelm A Bohr
Mar 2, 2017·World Journal of Gastroenterology : WJG·Hiroyuki MatsubayashiToru Shimosegawa
Sep 14, 2020·Clinical Breast Cancer·Constantinos SavvaArvind Arora
Jun 25, 2021·Frontiers in Oncology·Mahnaz NorouziMohammad Amin Tabatabaiefar

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