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Germline Mutations and Risk for Neoplastic Disease Progression During Pancreatic Surveillance

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Key Points

  • A previously unidentified deleterious mutation was found in 4.3% of individuals meeting surveillance criteria on the basis of family history.
  • The risk of pancreatic cancer, high-grade dysplasia, or worrisome features on imaging was significantly higher among individuals with germline mutations.

In a study reported in the Journal of Clinical Oncology, Abe et al found previously unidentified deleterious germline mutations in patients with family history as the basis for pancreatic surveillance. Moreover, the study showed the risk of pancreatic cancer was higher in individuals with germline mutations vs those meeting family history criteria for surveillance without known mutations.

The study included 464 high-risk individuals in the Cancer of the Pancreas Screening program at Johns Hopkins Hospital who were undergoing pancreatic surveillance; of these, 119 had a known deleterious germline mutation in a pancreatic cancer susceptibility gene, and 345 met family history criteria for pancreatic surveillance but had no known germline mutation. Next-generation sequencing was used to identify previously unrecognized germline mutations in these 345 individuals.

Risk Associated With Germline Mutations vs Family History

Overall, 15 (4.3%) of 345 individuals classified as having familial risk had a previously unrecognized pancreatic cancer susceptibility gene mutation, with 9 involving ATM; 2, BRCA2; 1, BRCA1; 1, PALB2; 1, TP53; and 1, CPA1. In analysis adjusted for age and sex and accounting for death as a competing event, the cumulative incidence of pancreatic cancer over 16 years was higher in the deleterious germline mutation group vs the familial risk group (hazard ratio [HR] = 2.85, 95% confidence interval [CI] = 1.0–8.2, P = .05). The likelihood of pancreatic cancer or high-grade dysplasia was also higher in the germline mutation group (HR = 2.81, P = .02), with elevated risk also observed when presence of clinically worrisome features on pancreatic imaging was included in the endpoint (HR = 3.13, P < .001).

The investigators concluded, “The cumulative incidence of pancreatic cancer is significantly higher among individuals with an identifiable deleterious germline mutation in a pancreatic cancer susceptibility gene than it is among individuals with a strong family history but no identified mutation. Gene testing of individuals who meet criteria for pancreatic surveillance on the basis of their family history may better define those most at risk for neoplastic progression.”

Michael Goggins, MD, of Johns Hopkins Medical Institutions, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the National Institutes of Health Grant, Susan Wojcicki and Dennis Troper, Pancreatic Cancer Action Network, and others. The study authors’ full disclosures can be found at jco.ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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