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Cancer. 2018 Apr 15;124(8):1691-1700. doi: 10.1002/cncr.31242. Epub 2018 Jan 23.

Germline mutation prevalence in individuals with pancreatic cancer and a history of previous malignancy.

Author information

1
Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
2
Castle Biosciences Incorporated, Friendswood, Texas.
3
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
4
Invitae Corporation, San Francisco, California.
5
Department of Hematology/Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
6
Department of Gastroenterology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Abstract

BACKGROUND:

Approximately 10% of pancreatic adenocarcinoma (PC) cases are attributed to hereditary causes. Individuals with PC and a personal history of another cancer associated with hereditary breast and ovarian cancer (HBOC) or Lynch syndrome (LS) may be more likely to carry germline mutations.

METHODS:

Participants with PC and a history of cancer were selected from a pancreatic disease registry. Of 1296 individuals with PC, 149 had a relevant history of cancer. If banked DNA was available, a multigene panel was performed for individuals who had not 1) previously had a mutation identified through clinical testing or 2) undergone clinical multigene panel testing with no mutations detected.

RESULTS:

Twenty-two of 124 individuals with PC and another HBOC- or LS-related cancer who underwent genetic testing had a mutation identified in a PC susceptibility gene (18%). If prostate cancer is excluded, the mutation prevalence increased to 23% (21/93). Mutation carriers were more likely to have more than 1 previous cancer diagnosis (P = .001), to have had clinical genetic testing (P = .001), and to meet National Comprehensive Cancer Network (NCCN) genetic testing criteria (P < .001). Approximately 23% of mutation carriers did not meet NCCN HBOC or LS testing guidelines based on their personal cancer history and reported cancer history in first-degree relatives.

CONCLUSION:

At least 18% of individuals with PC and a personal history of other HBOC- or LS-related cancers carry mutations in a PC susceptibility gene based on our data, suggesting that criteria for genetic testing in individuals with PC should include consideration of previous cancer history. Cancer 2018;124:1691-700. © 2018 American Cancer Society.

KEYWORDS:

Lynch syndrome; genetic testing; germline mutation; hereditary breast and ovarian cancer syndrome; pancreatic cancer

PMID:
29360161
DOI:
10.1002/cncr.31242
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