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Multicenter Study
. 2024 Oct 1;130(19):3297-3304.
doi: 10.1002/cncr.35383. Epub 2024 May 29.

The role of family history in predicting germline pathogenic variant carriers who develop pancreatic cancer: Results of a multicenter collaboration

Eve Karloski  1 , Beth Dudley  1 , Brenda Diergaarde  2 , Amie Blanco  3 , Jessica N Everett  4 , Elana Levinson  5 , Tara Rangarajan  6 , Peter P Stanich  7 , Kimberly Childers  8 , Sandra Brown  8 , Christine Drogan  9 , Giulia Martina Cavestro  10 , Kelly Gordon  8 , Aparajita Singh  11 , Diane M Simeone  12 , Hannah Reich  5 , Fay Kastrinos  13 , Dana Zakalik  6 , Heather Hampel  14 , Rachel Pearlman  14 , Ora K Gordon  8 , Sonia S Kupfer  9 , Marta Puzzono  10 , Raffaella Alessia Zuppardo  10 , Randall E Brand  1
Affiliations
Multicenter Study

The role of family history in predicting germline pathogenic variant carriers who develop pancreatic cancer: Results of a multicenter collaboration

Eve Karloski et al. 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.

Keywords: genetic testing; germline mutation; pancreatic cancer; risk factors.

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Conflict of interest statement

Conflict of Interest

Karloski, Dudley, Diergaarde, Everett, Levinson, Rangarajan, Childers, Brown, Drogan, Cavestro, K Gordon, Singh, Reich, Kastrinos, Zakalik, Pearlman, Kupfer, Puzzono, Zuppardo- no conflict of interest

Ms. Blanco’s spouse is a salaried employee for BioMarin.

Dr. Stanich receives research support from Emtora Biosciences, Freenome, Guardant Health, Janssen Pharmaceuticals Inc., Pfizer Inc., and the PTEN Research Foundation.

Dr. Simeone receives research funding from Tempus, Novartis, Micronoma, Clearnote health, and Biological Dynamics. She serves in an advisory capacity for Immunicom and Interpace.

Ms. Hampel is on the scientific advisory boards for GenomeMedical and Natera. She has stock/stock options in GenomeMedical and GI OnDemand. She does consulting for 23andMe, GI OnDemand, and Carelon.

Dr. O Gordon receives institutional research funding from Grail Inc and on scientific advisory boards for Genetic Technologies Corp and Grail Inc.

Dr. Brand receives research support from Freenome, Immunovia, and Radialis. He also serves on a scientific advisory board for Immunovia.

References

    1. NCI SEER Program Cancer Stat Facts: Pancreas Cancer, https://seer.cancer.gov/statfacts/html/pancreas.html; [accessed 16 June 2022].
    1. Rulyak SJ and Brentnall TA. Inherited pancreatic cancer: improvements in our understanding of genetics and screening. Int J Biochem Cell Biol. 2004; 36(8): 1386–1392. - PubMed
    1. Goldstein AM, Fraser MC, Struewing JP, et al. Increased risk of pancreatic cancer in melanoma-prone kindreds with p16INK4 mutations. N Engl J Med 1995; 333(15): 970–974. - PubMed
    1. Thompson D, Easton DF, and Breast Cancer Linkage Consortium. Cancer Incidence in BRCA1 mutation carriers. J Natl Cancer Inst. 2002; 94(18): 1358–1365. - PubMed
    1. Breast Cancer Linkage Consortium. Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst 1999; 91(15): 1310–1316. - PubMed

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