Parent-of-Origin-Aware Genomic Analysis to Enhance Cascade Testing in Pancreatic Cancer: A Population-Based Study

Identifying germline pathogenic variants has therapeutic value for pancreatic ductal adenocarcinoma (PDAC) patients and critical implications for cascade genetic testing in families, the latter being an increasing focus for public health genomic initiatives. We measured cascade testing rates for one hundred consecutive hereditary PDAC probands (March 2014-December 2023) and assessed the potential impact of using a novel technology, Parent-of-Origin-Aware genomic analysis (POAga) to enhance cascade testing. POAga requires a new blood sample and enables variant segregation to the maternal or paternal lineage. Thirteen probands were successfully contacted about POAga and nine provided a research blood sample. Parental origin was determined for all variants, and if applied at the time of diagnosis, would have immediately refined risk estimates for at least 188 relatives. POAga may overcome a major barrier to cascade testing in PDAC by clarifying which side of the family is at risk, improving cascade testing effectiveness and familial cancer prevention strategies.