Parent-of-Origin-Aware Genomic Analysis to Enhance Cascade Testing in Pancreatic Cancer: A Population-Based Study
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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.
What is known about the topic
Despite significant expansion in universal genetic testing criteria, cascade testing rates in relatives remain sub-optimal and require novel strategies in order to realize the full preventive value of hereditary cancer identification.
What this paper adds
This study describes the real-world impact of a new technological advance, Parent-of-Origin-Aware genomic analysis, that fundamentally changes genetic risk assessment by identifying which parental branch is most likely to harbour risk. In doing so, it immediately focuses genetic counselling efforts on one side of the family, with important implications for patients, families, and health-system implementation.
