Prospective Risk of Pancreatic Cancer in Familial Pancreatic Cancer Kindreds
Abstract
Individuals with a family history of pancreatic cancer have an increased risk of developing pancreatic cancer. Quantification of this risk provides a rational basis for cancer risk counseling and for screening for early pancreatic cancer. In a prospective registry-based study, we estimated the risk of pancreatic cancer in individuals with a family history of pancreatic cancer. Standardized incidence ratios were calculated by comparing the number of incident pancreatic cancers observed with those expected using Surveillance, Epidemiology and End Results (SEER) rates. Familial pancreatic cancer (FPC) kindreds were defined as kindreds having at least one pair of first-degree relatives with pancreatic cancer, and sporadic pancreatic cancer (SPC) kindreds as families without such an affected pair. Nineteen incident pancreatic cancers developed among 5,179 individuals from 838 kindreds (at baseline, 370 FPC kindreds and 468 SPC kindreds). Of these 5,179 individuals, 3,957 had at least one first-degree relative with pancreatic cancer and contributed 10,538 person-years of follow-up. In this group, the observed-to-expected rate of pancreatic cancer was significantly elevated in members of FPC kindreds [9.0; 95% confidence interval (CI), 4.5–16.1], but not in the SPC kindreds (1.8; 95% CI., 0.22–6.4). This risk in FPC kindreds was elevated in individuals with three (32.0; 95% CI, 10.2–74.7), two (6.4; CI, 1.8–16.4), or one (4.6; CI, 0.5–16.4) first-degree relative(s) with pancreatic cancer. Risk was not increased among 369 spouses and other genetically unrelated relatives. Risk was higher in smokers than in nonsmokers. Individuals with a strong family history of pancreatic cancer have a significantly increased risk of developing pancreatic cancer.
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In the familial cancer setting, defining high-risk and very high-risk groups has been done by counting the number of FDRs affected by PDAC, with 2 affected FDRs defining an HRG and 3 FDRs defining a vHRG.
“in the familial cancer setting, this has been done by counting the number of FDRs affected by PDAC, with 2 affected FDRs defining an HRG and 3 FDRs defining a vHRG.69”
From Artificial Intelligence and Early Detection of Pancreatic Cancer: 2020 Summative Review (2021) · cites this paper as [69]
The ENDPAC score further risk-stratifies NOD into below-average-risk, modest-risk group, and vHRG based on age, rapidity of rise of glucose, and change in weight in the 12 months before NOD date.
“The ENDPAC score further risk-stratifies NOD into below-average-risk, modest-risk group, and vHRG based on age, rapidity of rise of glucose, and change in weight in the 12 months before NOD date.68”
From Artificial Intelligence and Early Detection of Pancreatic Cancer: 2020 Summative Review (2021) · cites this paper as [68]
New-onset diabetes cohort with an ENDPAC score of ≥3 falls in the very high-risk category.
“New-onset diabetes cohort with an ENDPAC score of ≥3 falls in this category.68”
From Artificial Intelligence and Early Detection of Pancreatic Cancer: 2020 Summative Review (2021) · cites this paper as [68]
Subjects with NOD and ENDPAC score of >0 fall in the intermediate high-risk category.
“Subjects with NOD and Enriching New-onset Diabetes for Pancreatic Cancer (ENDPAC) score of >0 fall in this category.68”
From Artificial Intelligence and Early Detection of Pancreatic Cancer: 2020 Summative Review (2021) · cites this paper as [68]
For sporadic pancreatic cancer, there is currently only one HRG and that is glycemically defined NOD.
“For sporadic pancreatic cancer, there is currently only one HRG and that is glycemically defined NOD.68,71”
From Artificial Intelligence and Early Detection of Pancreatic Cancer: 2020 Summative Review (2021) · cites this paper as [68]
The Pancreatic Cancer Action Network is supporting the Early Detection Initiative to provide imaging to individuals with NOD that are further stratified by the ENDPAC clinical model.
“The Pancreatic Cancer Action Network is supporting the Early Detection Initiative to provide imaging to individuals with NOD that are further stratified by the ENDPAC clinical model.68”
From Artificial Intelligence and Early Detection of Pancreatic Cancer: 2020 Summative Review (2021) · cites this paper as [68]
The risk of PDAC increases with the number of affected first-degree relatives with pancreatic cancer and in those who carry a pathogenic germline variant in a pancreatic cancer susceptibility gene.
“The risk increases with the number of affected first-degree relatives with pancreatic cancer and in those who carry a pathogenic germline variant in a pancreatic cancer susceptibility gene.9-11”
From The Multicenter Cancer of Pancreas Screening Study: Impact on Stage and Survival (2022) · cites this paper as [10]
The PDAC risk in the familial group appears significant enough to warrant surveillance.
“This observation is consistent with previous reports that the PDAC risk in the familial group appears significant enough to warrant surveillance.9,10,14”
From The Multicenter Cancer of Pancreas Screening Study: Impact on Stage and Survival (2022) · cites this paper as [10]
The number of first- and second-degree relatives with pancreatic cancer can be used to quantify pancreatic cancer risk.
“The number of first- and second-degree relatives with pancreatic cancer can be used to quantify pancreatic cancer risk.”
The estimated lifetime risk of pancreatic cancer for an individual with two first-degree relatives with pancreatic cancer is about 8%.
“the estimated lifetime risk of developing pancreatic cancer for an individual with two first-degree relatives with pancreatic cancer is ~8%.”
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- Authors
- Klein, A. P., Brune, K. A., Petersen, G. M., Goggins, M., Tersmette, A. C., Offerhaus, G. J. A., Griffin, C., Cameron, J. L., Yeo, C. J., Kern, S., & Hruban, R. H.
- Affiliations
- National Institutes of Health (US)
- 2Departments of Pathology,
- Mayo Clinic (US)
- Amsterdam UMC Location University of Amsterdam (NL)
- Johns Hopkins University (US)
- ORCID
- Venue
- Cancer Research
- Published
- 2004-04-01
- Volume
- 64
- Issue
- 7
- Pages
- 2634-2638
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2158834319
- Cited by
- 678
- References
- 1
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 32 · 2023: 29 · 2022: 60 · 2021: 47 · 2020: 43 · 2019: 36 · 2018: 31 · 2017: 43 · 2016: 39 · 2015: 36 · 2014: 32 · 2013: 19 · 2012: 39
- FWCI
- 10.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- National Cancer Institute (P50CA102701, R01CA097075, P50CA062924, CA 62924)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Keywords
- pancreatic cancer, familial pancreatic cancer, hereditary cancer predisposition, first-degree relatives, cancer risk assessment, standardized incidence ratio, cancer risk counseling, pancreatic cancer screening, smoking, genetic susceptibility
- MeSH terms
- Adult, Aged, Female, Humans, Male, Middle Aged, Pancreatic Neoplasms, Prospective Studies, Risk Factors, Incidence, SEER Program, Genetic Predisposition to Disease
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