Pashayan, N;
Duffy, SW;
Neal, DE;
Hamdy, FC;
Donovan, JL;
Martin, RM;
Harrington, P;
... Pharoah, PD; + view all
(2015)
Implications of polygenic risk-stratified screening for prostate cancer on overdiagnosis.
Genetics in Medicine
, 17
pp. 789-795.
10.1038/gim.2014.192.
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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.
| Type: | Article |
|---|---|
| Title: | Implications of polygenic risk-stratified screening for prostate cancer on overdiagnosis |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/gim.2014.192 |
| Publisher version: | http://dx.doi.org/10.1038/gim.2014.192 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 3.0 Unported License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/ |
| Keywords: | Cancer screening, Diagnosis, Disease genetics, Prostate cancer |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Applied Health Research |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1461264 |
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