Pancreatic cancer as a sentinel for hereditary cancer predisposition

BMC Cancer

Erin L. Young¹  Russell Bell¹  Sean V. Tavtigian¹  Leigh Neumayer²  Amanda Gammon³  Wendy K. Kohlmann³  David E. Goldgar³  Bryony A. Thompson³  Deborah W. Neklason³  Sean J. Mulvihill³  Cathryn Koptiuch³  Theresa Werner³  Lisa A. Cannon-Albright³  Matthew A. Firpo³  Justin Berger⁴  Alison Fraser⁴ 

[1] Department of Oncological Sciences, University of Utah School of Medicine;Department of Surgery and Arizona Cancer Center, University of Arizona;Huntsman Cancer Institute, University of Utah School of Medicine;Population Sciences, Huntsman Cancer Institute, University of Utah;

关键词: HBOC;    Lynch syndrome;    Colorectal cancer;    Pancreatic cancer;    Genetic testing;   

DOI  :  10.1186/s12885-018-4573-5

来源: DOAJ

【 摘 要 】

Abstract Background 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.

【 授权许可】

Unknown