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Germline mutation prevalence in individuals with pancreatic cancer and a history of previous malignancy
Author(s) -
Dudley Beth,
Karloski Eve,
Monzon Federico A.,
Singhi Aatur D.,
Lincoln Stephen E.,
Bahary Nathan,
Brand Randall E.
Publication year - 2018
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.31242
Subject(s) - medicine , family history , cancer , genetic testing , pancreatic cancer , ovarian cancer , breast cancer , oncology , malignancy , germline mutation , mutation , lynch syndrome , brca mutation , adenocarcinoma , genetics , gene , colorectal cancer , biology , dna mismatch repair
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