Pancreatic cancer risk to siblings of probands in bilineal cancer settings

• Published in: Genetics in medicine Vol. 24; no. 5; pp. 1008 - 1016
• Main Authors: Rabe, Kari G., Stevens, Maria A., Hernández, Amanda Toledo, Chandra, Shruti, Hubbard, Joleen M., Kemppainen, Jennifer L., Majumder, Shounak, Petersen, Gloria M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-05-2022
• Subjects: Familial risk; Family; Genetic Predisposition to Disease; Humans; Pancreatic cancer; Pancreatic Neoplasms; Pancreatic Neoplasms - epidemiology; Pancreatic Neoplasms - genetics; Risk perception; Siblings; Familial risk; Pancreatic cancer; Risk perception
• ISSN: 1098-3600; 1530-0366
• DOI: 10.1016/j.gim.2022.01.016

Pancreatic cancer (PC) risk is increased in families, but PC risk and risk perception have been understudied when both parents have cancer.
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.
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.
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.