The role of family history in predicting germline pathogenic variant carriers who develop pancreatic cancer: Results of a multicenter collaboration.
Document Type
Article
Publication Date
10-1-2024
Publication Title
Cancer
Abstract
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) surveillance is recommended for some individuals with a pathogenic or likely pathogenic variant (PV/LPV) in a PDAC susceptibility gene; the recommendation is often dependent on family history of PDAC. This study aimed to describe PDAC family history in individuals with PDAC who underwent genetic testing to determine the appropriateness of including a family history requirement in these recommendations.
METHODS: Individuals with PDAC with a germline heterozygous PV/LPV in ATM, BRCA1, BRCA2, EPCAM, MLH1, MSH2, MSH6, PALB2, or PMS2 (PV/LPV carriers) were assessed for family history of PDAC in first-degree relatives (FDRs) or second-degree relatives (SDRs) from nine institutions. A control group of individuals with PDAC without a germline PV/LPV was also assessed.
RESULTS: The study included 196 PV/LPV carriers and 1184 controls. In the PV/LPV carriers, 25.5% had an affected FDR and/or SDR compared to 16.9% in the control group (p = .004). PV/LPV carriers were more likely to have an affected FDR compared to the controls (p = .003) but there was no statistical difference when assessing only affected SDRs (p = .344).
CONCLUSIONS: Most PV/LPV carriers who developed PDAC did not have a close family history of PDAC and would not have met most current professional societies' recommendations for consideration of PDAC surveillance before diagnosis. However, PV/LPV carriers were significantly more likely to have a family history of PDAC, particularly an affected FDR. These findings support family history as a risk modifier in PV/LPV carriers, and highlight the need to identify other risk factors.
Volume
130
Issue
19
First Page
3297
Last Page
3304
Recommended Citation
Karloski E, Dudley B, Diergaarde B, Blanco A, Everett JN, Levinson E, et al [Rangarajan T] The role of family history in predicting germline pathogenic variant carriers who develop pancreatic cancer: Results of a multicenter collaboration. Cancer. 2024 Oct 1;130(19):3297-3304. doi: 10.1002/cncr.35383. PMID: 38809542
DOI
10.1002/cncr.35383
ISSN
1097-0142
PubMed ID
38809542