Pancreatic cancer risk to siblings of probands in bilineal cancer settings

Abstract

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.

Keywords: Familial risk; Pancreatic cancer; Risk perception.

Figure 1.

Methods and Subject Recruitment. Pancreatic Cancer (PC) Probands were Sequentially Recruited into the Prospective Mayo Clinic Biospecimen Resource for Pancreas Research. Cancer Triads were Defined as a PC Proband and Two Parents with Cancer. Triad Groups were Stratified as Triad 1=no parent with PC; Triad 2=one parent with PC; and Triad 3=both parents with PC. At-Risk Siblings in Triads were Identified from Family History Surveys.

Figure 2.

Risk Perception and Concern of Getting Pancreatic Cancer (PC), Shown by Proportion of Respondents, Comparing Controls and At-Risk Siblings in Cancer Triads. Cancer Triads were Defined as a PC Proband and Two Parents with Cancer; Triad Groups were Stratified as Triad 1=no parent with PC; Triad 2=one parent with PC; and Triad 3=both parents with PC. (A) Comparative Risk, Perceived Risk, and Concern for Getting PC; (B) Thoughts about Chances of Getting PC and Impact on Mood and Daily Activities. Values within bars refer to proportion of responses for “High”, “Likely,” “Concerned,” and “Often,” respectively. All difference comparisons of at-siblings in triads to controls are statistically significant (p<=0.002).