Resumen
Prevalence and cancer risk estimates derived from the evaluation of affected individuals in the clinic are subject to ascertainment bias. This limitation can be mitigated using a genome-first approach in which genotypic data is analyzed before knowing a patient?s phenotype. Our study aimed to analyze two large cohorts with available exome and phenotype data unselected for a specific diagnosis from a genome-first perspective focusing on six pancreatic cancer predisposition genes. We provide estimates of (1) prevalence of heterozygotes for the general population and for individuals with pancreatic cancer and (2) cancer risk for pancreatic cancer for each gene evaluated. For mutation carriers, we found an elevated risk of pancreatic cancer for most genes evaluated, with variation among genes. This work expands our knowledge of the complex genetics of this cancer and will help identify patients at the highest risk who could benefit from future screening or therapeutic strategies.