Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Apr;17(2):235-245.
doi: 10.1007/s10689-017-0019-5.

The Spectrum of Genetic Variants in Hereditary Pancreatic Cancer Includes Fanconi Anemia Genes

Free PMC article

The Spectrum of Genetic Variants in Hereditary Pancreatic Cancer Includes Fanconi Anemia Genes

Thomas P Slavin et al. Fam Cancer. .
Free PMC article


Approximately 5-10% of all pancreatic cancer patients carry a predisposing mutation in a known susceptibility gene. Since >90% of patients present with late stage disease, it is crucial to identify high risk individuals who may be amenable to early detection or other prevention. To explore the spectrum of hereditary pancreatic cancer susceptibility, we evaluated germline DNA from pancreatic cancer participants (n = 53) from a large hereditary cancer registry. For those without a known predisposition mutation gene (n = 49), germline next generation sequencing was completed using targeted capture for 706 candidate genes. We identified 16 of 53 participants (30%) with a pathogenic (P) or likely pathogenic (LP) variant that may be related to their hereditary pancreatic cancer predisposition; seven had mutations in genes associated with well-known cancer syndromes (13%) [ATM (2), BRCA2 (3), MSH2 (1), MSH6 (1)]. Many had mutations in Fanconi anemia complex genes [BRCA2 (3 participants), FANCF, FANCM]. Eight participants had rare protein truncating variants of uncertain significance with no other P or LP variants. Earlier age of pancreatic cancer diagnosis (57.5 vs 64.8 years) was indicative of possessing a P or LP variant, as was cancer family history (p values <0.0001). Our multigene panel approach for identifying known cancer predisposing genetic susceptibility in those at risk for hereditary pancreatic cancer may have direct applicability to clinical practice in cases with mutations in actionable genes. Future pancreatic cancer predisposition studies should include evaluation of the Fanconi anemia genes.

Keywords: BRCA2; Germline; Hereditary; Pancreatic cancer; Susceptibility.

Conflict of interest statement


The authors declare that they have no conflicts of interest.


Figure 1
Figure 1. Clinical Cancer Genomics Cancer Research Network Participating Site Locations
Markers represent Clinical Cancer Genomics Community Research Network participating site locations. See Supplemental Table 1 for a complete site list and site origin for enrolled participants from this study.

Similar articles

See all similar articles

Cited by 6 articles

See all "Cited by" articles

Publication types

MeSH terms