Pancreatic cancer-associated gene polymorphisms in a nation-wide cohort of p16-Leiden germline mutation carriers; a case–control study
Open accessAbstract
BACKGROUND: The p16-Leiden founder mutation in the CDKN2A gene is the most common cause of Familial Atypical Multiple Mole Melanoma (FAMMM) syndrome in the Netherlands. Individuals with this mutation are at increased risk for developing melanoma of the skin, as well as pancreatic cancer. However, there is a notable interfamilial variability in the occurrence of pancreatic cancer among p16-Leiden families. We aimed to test whether previously identified genetic risk factors for pancreatic cancer modify the risk for pancreatic cancer in p16-Leiden germline mutation carriers. METHODS: Seven pancreatic cancer-associated SNPs were selected from the literature and were genotyped in a cohort of 185 p16-Leiden germline mutation carriers from 88 families, including 50 cases (median age 55 years) with pancreatic cancer and 135 controls (median age 64 years) without pancreatic cancer. Allelic odds ratios per SNP were calculated. RESULTS: No significant association with pancreatic cancer was found for any of the seven SNPs. CONCLUSIONS: Since genetic modifiers for developing melanoma have already been identified in CDKN2A mutation carriers, this study does not exclude that genetic modifiers do not play a role in the individual pancreatic cancer risk in this cohort of p16-Leiden germline mutation carriers. The search for these modifiers should therefore continue, because they can potentially facilitate more targeted pancreatic surveillance programs.
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Sixteen percent of p16-Leiden mutation carriers with pancreatic cancer were diagnosed at age <45.
“16% of p16-Leiden mutation carriers with pancreatic cancer were diagnosed at age <4550”
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- Authors
- Potjer, T. P., van der Stoep, N., Houwing-Duistermaat, J. J., Konings, I. C. A. W., Aalfs, C. M., van den Akker, P. C., Ausems, M. G., Dommering, C. J., van der Kolk, L. E., Maiburg, M. C., Spruijt, L., Wagner, A., Vasen, H. F. A., & Hes, F. J.
- Affiliations
- Leiden University Medical Center (NL)
- Erasmus MC (NL)
- Amsterdam UMC Location University of Amsterdam (NL)
- University Medical Center Utrecht (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Maastricht University Medical Centre (NL)
- Radboud University Medical Center (NL)
- Corresponding author
- Potjer, Thomas P
- ORCID
- Venue
- BMC Research Notes
- Published
- 2015-06-26
- Volume
- 8
- Issue
- 1
- Pages
- 264-264
- ISSN
- 1756-0500 (ISSN-L)
- PMC
- PMC4480449
- OpenAlex
- W1571980651
- Cited by
- 15
- References
- 20
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 2
- FWCI
- 0.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMC Research Notes (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
- Radboud Repository (Radboud University) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- 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, CDKN2A, germline mutation carriers, single nucleotide polymorphisms, genetic risk factors, genetic modifiers, familial atypical multiple mole melanoma syndrome, pancreatic cancer surveillance
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alleles, Dysplastic Nevus Syndrome, Female, Heterozygote, Humans, Male, Melanoma, Middle Aged, Netherlands, Pancreatic Neoplasms, Pedigree, Risk Factors, Skin Neoplasms, Odds Ratio, Case-Control Studies, Germ-Line Mutation, Cyclin-Dependent Kinase Inhibitor p16, Polymorphism, Single Nucleotide
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