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Understanding familial risk of pancreatic ductal adenocarcinoma

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease that is the result of an accumulation of sequential genetic alterations. These genetic alterations can either be inherited, such as pathogenic germline variants that are associated with an increased risk of cancer, or acquired, such as somatic mutations that occur during the lifetime of an individual. Understanding the genetic basis of inherited risk of PDAC is essential to advancing patient care and outcomes through improved clinical surveillance, early detection initiatives, and targeted therapies. In this review we discuss factors associated with an increased risk of PDAC, the prevalence of genetic variants associated with an increased risk in patients with PDAC, estimates of PDAC risk in carriers of pathogenic germline variants in genes associated with an increased risk of PDAC. The role of common variants in pancreatic cancer risk will also be discussed.

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Funding

This work was supported by: The Sol Goldman Pancreatic Cancer Research Center; Susan Wojcicki and Dennis Troper; The Lustgarten Foundation; The Rolfe Pancreatic Cancer Foundation; NIH/NCI P50 CA62924; DOD W81XWH2210325.

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  1. Alison P. Klein and Nicholas J. Roberts contributed equally to this work.

Authors and Affiliations

  1. The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Raymond M. Paranal, Laura D. Wood, Alison P. Klein & Nicholas J. Roberts

  2. Human Genetics Predoctoral Training Program, the McKusick-Nathans Department of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Raymond M. Paranal

  3. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Laura D. Wood, Alison P. Klein & Nicholas J. Roberts

  4. Department of Epidemiology, Johns Hopkins University School of Public Health, Baltimore, MD, USA

    Alison P. Klein

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Contributions: (I) Conception and design: All authors; (II) Administrative support: None; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: All authors; (V) Data analysis and interpretation: None; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

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Paranal, R.M., Wood, L.D., Klein, A.P. et al. Understanding familial risk of pancreatic ductal adenocarcinoma. Familial Cancer (2024). https://doi.org/10.1007/s10689-024-00383-2

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