Familial pancreatic cancer--current knowledge

Nat Rev Gastroenterol Hepatol. 2012 Aug;9(8):445-53. doi: 10.1038/nrgastro.2012.111. Epub 2012 Jun 5.

Abstract

Familial pancreatic cancer (FPC) describes families with at least two first-degree relatives with confirmed exocrine pancreatic cancer that do not fulfil the criteria of other inherited tumour syndromes with increased risks of pancreatic cancer, such as Peutz-Jeghers syndrome, hereditary pancreatitis, and hereditary breast and ovarian cancer. The inheritance of FPC is mostly autosomal dominant and with a heterogeneous phenotype. The major gene defect is yet to be identified, although germline mutations in BRCA2, PALB2 and ATM are causative in some FPC families. Expert consensus conferences considered it appropriate to screen for pancreatic cancer in high-risk individuals using a multidisciplinary approach under research protocol conditions. However, neither biomarkers nor reliable imaging modalities for the detection of high-grade precursor lesions are yet available. Most screening programmes are currently based on findings from endoscopic ultrasonography and MRI, and data has demonstrated that precursor lesions of pancreatic cancer can be identified. No consensus exists regarding the age to initiate or stop screening and the optimal intervals for follow-up. Timing and extent of surgery as a treatment for FPC are debated. This Review focuses on the clinical phenotype of FPC, its histopathological characteristics, known underlying genetic changes and associated genetic counselling and screening.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor / analysis
  • Carcinoma / genetics*
  • Genes, BRCA1 / physiology
  • Genetic Counseling
  • Genetic Predisposition to Disease
  • Germ-Line Mutation
  • Humans
  • Melanoma / genetics
  • Neoplastic Syndromes, Hereditary / genetics
  • Pancreatic Neoplasms / genetics*
  • Phenotype

Substances

  • Biomarkers, Tumor

Supplementary concepts

  • Melanoma-Pancreatic Cancer Syndrome
  • Pancreatic carcinoma, familial