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Cited by 65Pancreatic and Hepatic Oncology ResearchBRCA gene mutations in cancerGenetic factors in colorectal cancer

The Role of Inherited Pathogenic CDKN2A Variants in Susceptibility to Pancreatic Cancer

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Kimura, Hirokazu, Klein, Alison P., Hruban, Ralph H., Roberts, Nicholas J.·2021·Pancreas
DOI 10.1097/mpa.0000000000001888PMC PMC8562885
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Abstract

CDKN2A is cell cycle negative regulator, and the role of CDKN2A in the development of pancreatic ductal adenocarcinoma, which continues to be a lethal cancer, is well-established. Somatic loss of CDKN2A is considered one of the major drivers of pancreatic tumorigenesis. CDKN2A gene is one of the pancreatic cancer susceptibility gene; in addition to melanoma, pathogenic germline CDKN2A variants have been identified in up to 3.3% patients with pancreatic ductal adenocarcinoma depending on family history of disease. Carriers of a known pathogenic germline CDKN2A variant have up to a 12.3-fold increased risk of developing pancreatic cancer. Recently, several studies have demonstrated the benefit of clinical surveillance in patients with pathogenic germline CDKN2A variants. Therefore, identification of patients with a pathogenic germline CDKN2A variant is important for screening of at-risk relatives for pancreatic cancer. It has the potential to lead to the detection of early, potentially curable pancreatic cancer and precursor neoplasms, and reduce mortality. Furthermore, patients with a germline pathogenic CDKN2A variant and somatic loss of CDKN2A may benefit in the future from treatment with targeted therapies, such as a CDK4/6 inhibitor.

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  • Inherited pathogenic variants in CDKN2A contribute significantly to pancreatic cancer susceptibility, especially in FAMMM syndrome families.

    “Inherited pathogenic variants in the CDKN2A gene contribute significantly to pancreatic cancer susceptibility, especially in FAMMM syndrome families.”

    From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [60]

  • The risk of PDAC increases in individuals with pathogenic germline CDKN2A variants, even without a family history of melanoma.

    “The risk of PDAC increases in individuals with pathogenic germline CDKN2A variants, even without a family history of melanoma.”

    From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [60]

  • CDKN2A variant carriers face increased risk not only for PDAC but also for melanoma and various other cancers.

    “CDKN2A variant carriers face an increased risk not only for PDAC but also for melanoma and various other cancers.”

    From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [60]

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Cited by

Sorted by citations

Authors
Kimura, H., Klein, A. P., Hruban, R. H., & Roberts, N. J.
Affiliations
  • Sol Goldman Pancreatic Cancer Research Center, Department of Pathology
  • Johns Hopkins University (US)
Corresponding author
  • Kimura, Hirokazu
  • Klein, Alison P.
  • Hruban, Ralph H.
  • Roberts, Nicholas J.
ORCID
Venue
Pancreas
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2021-09
Volume
50
Issue
8
Pages
1123-1130
ISSN
  • 0885-3177 (ISSN-L)
  • 1536-4828
DOI
10.1097/mpa.0000000000001888
PMC
PMC8562885
OpenAlex
W3209449223
Cited by
65
References
13
Citations by year
2026: 12 · 2025: 17 · 2024: 16 · 2023: 12 · 2022: 8
FWCI
1.09
Type
journal article
Language
en
Open access
Locations
  • Pancreas (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Cancer Institute (R00CA190889, P50CA062924)
Topics
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Keywords
CDKN2A, germline pathogenic variants, pancreatic ductal adenocarcinoma, hereditary cancer predisposition, pancreatic cancer risk, clinical surveillance, family screening, CDK4/6 inhibitors, targeted therapy
MeSH terms
Humans, Pancreatic Neoplasms, Risk, Genetic Variation, Germ-Line Mutation, Cyclin-Dependent Kinase Inhibitor p16, Genetic Predisposition to Disease, Carcinoma, Pancreatic Ductal

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