Implications of polygenic risk-stratified screening for prostate cancer on overdiagnosis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-10

AUTHORS

Nora Pashayan, Stephen W. Duffy, David E. Neal, Freddie C. Hamdy, Jenny L. Donovan, Richard M. Martin, Patricia Harrington, Sara Benlloch, Ali Amin Al Olama, Mitul Shah, Zsofia Kote-Jarai, Douglas F. Easton, Rosalind Eeles, Paul D. Pharoah

ABSTRACT

PURPOSE: This study aimed to quantify the probability of overdiagnosis of prostate cancer by polygenic risk. METHODS: We calculated the polygenic risk score based on 66 known prostate cancer susceptibility variants for 17,012 men aged 50-69 years (9,404 men identified with prostate cancer and 7,608 with no cancer) derived from three UK-based ongoing studies. We derived the probabilities of overdiagnosis by quartiles of polygenic risk considering that the observed prevalence of screen-detected prostate cancer is a combination of underlying incidence, mean sojourn time (MST), test sensitivity, and overdiagnosis. RESULTS: Polygenic risk quartiles 1 to 4 comprised 9, 18, 25, and 48% of the cases, respectively. For a prostate-specific antigen test sensitivity of 80% and MST of 9 years, 43, 30, 25, and 19% of the prevalent screen-detected cancers in quartiles 1 to 4, respectively, were likely to be overdiagnosed cancers. Overdiagnosis decreased with increasing polygenic risk, with 56% decrease between the lowest and the highest polygenic risk quartiles. CONCLUSION: Targeting screening to men at higher polygenic risk could reduce the problem of overdiagnosis and lead to a better benefit-to-harm balance in screening for prostate cancer. More... »

PAGES

789

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/gim.2014.192

DOI

http://dx.doi.org/10.1038/gim.2014.192

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1000059569

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25569441


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