Beth Dudley1, Eve Karloski1, Federico A Monzon2, Aatur D Singhi3, Stephen E Lincoln4, Nathan Bahary5, Randall E Brand6. 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.
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.
Authors: Carol Cremin; Michael Kuan-Ching Lee; Quan Hong; Carolyn Hoeschen; Anna Mackenzie; Katherine Dixon; Mary McCullum; Jennifer Nuk; Steve Kalloger; Joanna Karasinska; Charles Scudamore; Peter T W Kim; Fergal Donnellan; Eric C S Lam; Howard J Lim; Cynthia L Neben; Will Stedden; Alicia Y Zhou; David F Schaeffer; Sophie Sun; Daniel J Renouf; Kasmintan A Schrader Journal: Cancer Med Date: 2020-04-07 Impact factor: 4.452