Pancreatic cancer as a sentinel for hereditary cancer predisposition
AuthorYoung, Erin L.
Thompson, Bryony A.
Neklason, Deborah W.
Firpo, Matthew A.
Kohlmann, Wendy K.
Goldgar, David E.
Mulvihill, Sean J.
Cannon-Albright, Lisa A.
Tavtigian, Sean V.
AffiliationUniv Arizona, Arizona Canc Ctr
MetadataShow full item record
CitationYoung, E. L., Thompson, B. A., Neklason, D. W., Firpo, M. A., Werner, T., Bell, R., ... & Kohlmann, W. K. (2018). Pancreatic cancer as a sentinel for hereditary cancer predisposition. BMC cancer, 18(1), 697. https://doi.org/10.1186/s12885-018-4573-5
Rights© The Author(s). 2018. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractBackground: Genes associated with hereditary breast and ovarian cancer (HBOC) and colorectal cancer (CRC) predisposition have been shown to play a role in pancreatic cancer susceptibility. Growing evidence suggests that pancreatic cancer may be useful as a sentinel cancer to identify families that could benefit from HBOC or CRC surveillance, but to date pancreatic cancer is only considered an indication for genetic testing in the context of additional family history. Methods: Preliminary data generated at the Huntsman Cancer Hospital (HCH) included variants identified on a custom 34-gene panel or 59-gene panel including both known HBOC and CRC genes for respective sets of 66 and 147 pancreatic cancer cases, unselected for family history. Given the strength of preliminary data and corresponding literature, 61 sequential pancreatic cancer cases underwent a custom 14-gene clinical panel. Sequencing data from HCH pancreatic cancer cases, pancreatic cancer cases of the Cancer Genome Atlas (TCGA), and an unselected pancreatic cancer screen from the Mayo Clinic were combined in a meta-analysis to estimate the proportion of carriers with pathogenic and high probability of pathogenic variants of uncertain significance (HiP-VUS). Results: Approximately 8.6% of unselected pancreatic cancer cases at the HCH carried a variant with potential HBOC or CRC screening recommendations. A meta-analysis of unselected pancreatic cancer cases revealed that approximately 11.5% carry a pathogenic variant or HiP-VUS. Conclusion: With the inclusion of both HBOC and CRC susceptibility genes in a panel test, unselected pancreatic cancer cases act as a useful sentinel cancer to identify asymptomatic at-risk relatives who could benefit from relevant HBOC and CRC surveillance measures.
NoteOpen access journal.
VersionFinal published version
SponsorsUnited States National Institutes of Health (NIH) National Cancer Institute (NCI) [R01CA164138]; NCI [P30CA042014]; Utah Genome Project; Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer program; Government of Canada through Genome Canada; Canadian Institutes of Health Research; Ministere de l'enseignement superieur, de la recherche, de la science, et de la technologie du Quebec through Genome Quebec; NIH NCI Cancer Center Support Grant [P30CA042014]; Huntsman Cancer Foundation; National Human Genome Research Institute [T32HG008962]
- Clinical Actionability of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Risk Assessment.
- Authors: Desmond A, Kurian AW, Gabree M, Mills MA, Anderson MJ, Kobayashi Y, Horick N, Yang S, Shannon KM, Tung N, Ford JM, Lincoln SE, Ellisen LW
- Issue date: 2015 Oct
- [Current clinical issues and recent trends in hereditary breast and ovarian cancer in Japan-genetic testing for HBOC and risk-reducing surgery].
- Authors: Arai M, Iwase T, Takazawa Y, Takeshima N
- Issue date: 2014 Nov
- Population-based genetic testing of asymptomatic women for breast and ovarian cancer susceptibility.
- Authors: Rowley SM, Mascarenhas L, Devereux L, Li N, Amarasinghe KC, Zethoven M, Lee JEA, Lewis A, Morgan JA, Limb S, Young MA, James PA, Trainer AH, Campbell IG
- Issue date: 2019 Apr
- Statewide Retrospective Review of Familial Pancreatic Cancer in Delaware, and Frequency of Genetic Mutations in Pancreatic Cancer Kindreds.
- Authors: Catts ZA, Baig MK, Milewski B, Keywan C, Guarino M, Petrelli N
- Issue date: 2016 May
- Cancer Predisposition Cascade Screening for Hereditary Breast/Ovarian Cancer and Lynch Syndromes in Switzerland: Study Protocol.
- Authors: Katapodi MC, Viassolo V, Caiata-Zufferey M, Nikolaidis C, Bührer-Landolt R, Buerki N, Graffeo R, Horváth HC, Kurzeder C, Rabaglio M, Scharfe M, Urech C, Erlanger TE, Probst-Hensch N, Heinimann K, Heinzelmann-Schwarz V, Pagani O, Chappuis PO
- Issue date: 2017 Sep 20