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The clinical utility and costs of whole-genome sequencing to detect cancer susceptibility variants—a multi-site prospective cohort study

2023; BioMed Central; Volume: 15; Issue: 1 Linguagem: Inglês

10.1186/s13073-023-01223-1

1756-994X

Aimee L. Davidson, Uwe Dressel, Sarah Norris, Daffodil M. Canson, Dylan M. Glubb, Cristina Fortuño, Georgina E. Hollway, Michael T. Parsons, Miranda E. Vidgen, Oliver Holmes, Lambros T. Koufariotis, Vanessa Lakis, Conrad Leonard, Scott Wood, Qinying Xu, Amy E. McCart Reed, Hilda A. Pickett, Mohammad Al-Shinnag, Rachel L. Austin, Jo Burke, Elisa J. Cops, Cassandra Nichols, Annabel Goodwin, Marion Harris, Megan Higgins, Emilia Ip, Cathy Kiraly‐Borri, Chiyan Lau, Julia Mansour, Michael W. Millward, Melissa Monnik, Nicholas Pachter, Abiramy Ragunathan, Rachel Susman, Sharron Townshend, Alison H. Trainer, Simon L. Troth, Kathy Tucker, Mathew Wallis, Maie Walsh, Rachel Williams, Ingrid Winship, Felicity Newell, Emma Tudini, John V. Pearson, Nicola Poplawski, Helen G. Mar Fan, Paul A. James, Amanda B. Spurdle, Nicola Waddell, Robyn L. Ward,

Genetic factors in colorectal cancer

Many families and individuals do not meet criteria for a known hereditary cancer syndrome but display unusual clusters of cancers. These families may carry pathogenic variants in cancer predisposition genes and be at higher risk for developing cancer.This multi-centre prospective study recruited 195 cancer-affected participants suspected to have a hereditary cancer syndrome for whom previous clinical targeted genetic testing was either not informative or not available. To identify pathogenic disease-causing variants explaining participant presentation, germline whole-genome sequencing (WGS) and a comprehensive cancer virtual gene panel analysis were undertaken.Pathogenic variants consistent with the presenting cancer(s) were identified in 5.1% (10/195) of participants and pathogenic variants considered secondary findings with potential risk management implications were identified in another 9.7% (19/195) of participants. Health economic analysis estimated the marginal cost per case with an actionable variant was significantly lower for upfront WGS with virtual panel ($8744AUD) compared to standard testing followed by WGS ($24,894AUD). Financial analysis suggests that national adoption of diagnostic WGS testing would require a ninefold increase in government annual expenditure compared to conventional testing.These findings make a case for replacing conventional testing with WGS to deliver clinically important benefits for cancer patients and families. The uptake of such an approach will depend on the perspectives of different payers on affordability.