Importance of Age of Onset in Pancreatic Cancer Kindreds
Open accessAbstract
BACKGROUND: Young-onset cancer is a hallmark of many familial cancer syndromes, yet the implications of young-onset disease in predicting risk of pancreatic cancer among familial pancreatic cancer (FPC) kindred members remain unclear. METHODS: To understand the relationship between age at onset of pancreatic cancer and risk of pancreatic cancer in kindred members, we compared the observed incidence of pancreatic cancer in 9040 individuals from 1718 kindreds enrolled in the National Familial Pancreas Tumor Registry with that observed in the general US population (Surveillance, Epidemiology, and End Results). Standardized incidence ratios (SIRs) were calculated for data stratified by familial vs sporadic cancer kindred membership, number of affected relatives, youngest age of onset among relatives, and smoking status. Competing risk survival analyses were performed to examine the risk of pancreatic cancer and risk of death from other causes according to youngest age of onset of pancreatic cancer in the family and the number of affected relatives. RESULTS: Risk of pancreatic cancer was elevated in both FPC kindred members (SIR = 6.79, 95% confidence interval [CI] = 4.54 to 9.75, P < .001) and sporadic pancreatic cancer (SPC) kindred members (SIR = 2.41, 95% CI = 1.04 to 4.74, P = .04) compared with the general population. The presence of a young-onset patient (<50 years) in the family did not alter the risk for SPC kindred members (SIR = 2.74, 95% CI = 0.05 to 15.30, P = .59) compared with those without a young-onset case in the kindred (SIR = 2.36, 95% CI = 0.95 to 4.88, P = .06). However, risk was higher among members of FPC kindreds with a young-onset case in the kindred (SIR = 9.31, 95% CI = 3.42 to 20.28, P < .001) than those without a young-onset case in the kindred (SIR = 6.34, 95% CI = 4.02 to 9.51, P < .001). Competing risk survival analyses indicated that the lifetime risk of pancreatic cancer in FPC kindreds increased with decreasing age of onset in the kindred (hazard ratio = 1.55, 95% CI = 1.19 to 2.03 per year). However, youngest age of onset for pancreatic cancer in the kindred did not affect the risk among SPC kindred members. CONCLUSIONS: Individuals with a family history of pancreatic cancer are at a statistically significantly increased risk of developing pancreatic cancer. Having a member of the family with a young-onset pancreatic cancer confers an added risk in FPC kindreds.
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Most pancreatic surveillance programmes lower the age at which surveillance is initiated for individuals with a first-degree relative with young-onset pancreatic cancer (age <50).
“Most pancreatic surveillance programmes lower the age at which surveillance is initiated for individuals with a first-degree relative with young-onset pancreatic cancer (age <50).”
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- Authors
- Brune, K. A., Lau, B., Palmisano, E., Canto, M., Goggins, M. G., Hruban, R. H., & Klein, A. P.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Klein, A. P.
- Venue
- JNCI Journal of the National Cancer Institute
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-01-12
- Volume
- 102
- Issue
- 2
- Pages
- 119-126
- ISSN
- 0027-8874 (ISSN-L)
- 1460-2105
- PMC
- PMC2808346
- OpenAlex
- W2142268074
- Cited by
- 257
- References
- 44
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 19 · 2023: 24 · 2022: 46 · 2021: 24 · 2020: 13 · 2019: 21 · 2018: 11 · 2017: 13 · 2016: 14 · 2015: 16 · 2014: 10 · 2013: 11 · 2012: 11
- FWCI
- 5.54
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- JNCI Journal of the National Cancer Institute (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Institutes of Health (CA62924, K01-AI071754)
- National Cancer Institute (K01-AI071754, P50CA062924, CA 62924)
- National Institute of Allergy and Infectious Diseases (K01AI071754)
- 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, young-onset cancer, age of onset, sporadic pancreatic cancer, standardized incidence ratio, lifetime cancer risk, smoking, hereditary cancer, cancer screening, cancer survivorship
- MeSH terms
- Adult, Aged, Female, Humans, Male, Middle Aged, Pancreatic Neoplasms, United States, Incidence, Odds Ratio, Age of Onset, SEER Program, Genetic Predisposition to Disease
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