TY - JOUR
T1 - Pancreatic cancer risk to siblings of probands in bilineal cancer settings
AU - Rabe, Kari G.
AU - Stevens, Maria A.
AU - Hernández, Amanda Toledo
AU - Chandra, Shruti
AU - Hubbard, Joleen M.
AU - Kemppainen, Jennifer L.
AU - Majumder, Shounak
AU - Petersen, Gloria M.
N1 - Funding Information:
Funding support for this study includes National Institutes of Health grants P50CA102701 for the Mayo Clinic Specialized Project Of Research Excellence (SPORE) in Pancreatic Cancer, R01CA97075, R01CA154517, U01CA210138, and the Rolfe Foundation for Pancreatic Research. The authors thank the patients and their families; the Cancer Risk Estimates Related to Susceptibility Genes (CARRIERS) study; and study assistants Bridget Rathbun, Cassandra Bell, Jennifer Brooks, Sarah Fagan, Christen Archer, Wyatt Anians, Margaret Meyer, and Megan Reichmann for their contributions to the study. Conceptualization: K.G.R. M.A.S. G.M.P.; Data Curation: K.G.R.; Formal Analysis: K.G.R. M.A.S. A.T.H.; Funding Acquisition: G.M.P.; Methodology: K.G.R. M.A.S. G.M.P.; Writing-original draft: K.G.R. M.A.S. G.M.P.; Writing-review and editing: A.T.H. S.C. J.M.H. J.L.K. S.M. The study was reviewed and approved by the Mayo Clinic Institutional Review Board (IRB). Mayo participants in this study provided informed written consent to research under IRB-approved protocols. The Mayo Clinic IRB is in compliance with the requirements of Food and Drug Administration regulations 21 Code of Federal Regulations (CFR) Parts 50 and 56 and Health and Human Services (HHS) regulations 45 CFR 46, which are guided by the Belmont Report. Data were not de-identified for analyses.
Funding Information:
Funding support for this study includes National Institutes of Health grants P50CA102701 for the Mayo Clinic Specialized Project Of Research Excellence (SPORE) in Pancreatic Cancer, R01CA97075, R01CA154517, U01CA210138, and the Rolfe Foundation for Pancreatic Research. The authors thank the patients and their families; the Cancer Risk Estimates Related to Susceptibility Genes (CARRIERS) study; and study assistants Bridget Rathbun, Cassandra Bell, Jennifer Brooks, Sarah Fagan, Christen Archer, Wyatt Anians, Margaret Meyer, and Megan Reichmann for their contributions to the study.
Publisher Copyright:
© 2022 American College of Medical Genetics and Genomics
PY - 2022/5
Y1 - 2022/5
N2 - Purpose: Pancreatic cancer (PC) risk is increased in families, but PC risk and risk perception have been understudied when both parents have cancer. Methods: An unbiased method defining cancer triads (proband with PC and both parents with cancer) in a prospective registry estimated risk of PC to probands’ siblings in triad group 1 (no parent with PC), group 2 (1 parent with PC), and group 3 (both parents with PC). We estimated standardized incidence ratios (SIRs) using a Surveillance, Epidemiology, and End Results (SEER) reference. We also estimated the risk when triad probands carried germline pathogenic/likely pathogenic variants in any of the 6 PC-associated genes (ATM, BRCA1, BRCA2, CDKN2A, MLH1, and TP53). PC risk perception/concern was surveyed in siblings and controls. Results: Risk of PC was higher (SIR = 3.5; 95% CI = 2.2-5.2) in 933 at-risk siblings from 297 triads. Risk increased by triad group: 2.8 (95% CI = 1.5-4.5); 4.5 (95% CI = 1.6-9.7); and 21.2 (95% CI = 4.3-62.0). SIR in variant-negative triads was 3.0 (95% CI = 1.6-5.0), whereas SIR in variant-positive triads was 10.0 (95% CI = 3.2-23.4). Siblings’ perceived risk/concern of developing PC increased by triad group. Conclusion: Sibling risks were 2.8- to 21.2-fold higher than that of the general population. Positive variant status increased the risk in triads. Increasing number of PC cases in a triad was associated with increased concern and perceived PC risk.
AB - Purpose: Pancreatic cancer (PC) risk is increased in families, but PC risk and risk perception have been understudied when both parents have cancer. Methods: An unbiased method defining cancer triads (proband with PC and both parents with cancer) in a prospective registry estimated risk of PC to probands’ siblings in triad group 1 (no parent with PC), group 2 (1 parent with PC), and group 3 (both parents with PC). We estimated standardized incidence ratios (SIRs) using a Surveillance, Epidemiology, and End Results (SEER) reference. We also estimated the risk when triad probands carried germline pathogenic/likely pathogenic variants in any of the 6 PC-associated genes (ATM, BRCA1, BRCA2, CDKN2A, MLH1, and TP53). PC risk perception/concern was surveyed in siblings and controls. Results: Risk of PC was higher (SIR = 3.5; 95% CI = 2.2-5.2) in 933 at-risk siblings from 297 triads. Risk increased by triad group: 2.8 (95% CI = 1.5-4.5); 4.5 (95% CI = 1.6-9.7); and 21.2 (95% CI = 4.3-62.0). SIR in variant-negative triads was 3.0 (95% CI = 1.6-5.0), whereas SIR in variant-positive triads was 10.0 (95% CI = 3.2-23.4). Siblings’ perceived risk/concern of developing PC increased by triad group. Conclusion: Sibling risks were 2.8- to 21.2-fold higher than that of the general population. Positive variant status increased the risk in triads. Increasing number of PC cases in a triad was associated with increased concern and perceived PC risk.
KW - Familial risk
KW - Pancreatic cancer
KW - Risk perception
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UR - http://www.scopus.com/inward/citedby.url?scp=85125361868&partnerID=8YFLogxK
U2 - 10.1016/j.gim.2022.01.016
DO - 10.1016/j.gim.2022.01.016
M3 - Article
C2 - 35227607
AN - SCOPUS:85125361868
SN - 1098-3600
VL - 24
SP - 1008
EP - 1016
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 5
ER -