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Genet Med. 2015 Oct;17(10):789-95. doi: 10.1038/gim.2014.192. Epub 2015 Jan 8.

Implications of polygenic risk-stratified screening for prostate cancer on overdiagnosis.

Author information

1
Department of Applied Health Research, University College London, London, UK.
2
Centre for Cancer Prevention, Mathematics and Statistics, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.
3
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
4
Nuffield Department of Surgery, Oxford John Radcliffe Hospital, University of Oxford, Headington, Oxford, UK.
5
School of Social and Community Medicine, University of Bristol, Bristol, UK.
6
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge, UK.
7
Department of Oncology, Strangeways Research Laboratory, University of Cambridge, Cambridge, UK.
8
Division of Genetics and Epidemiology, Institute of Cancer Research & Royal Marsden NHS Foundation Trust, London, UK.

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.

PMID:
25569441
PMCID:
PMC4430305
DOI:
10.1038/gim.2014.192
[Indexed for MEDLINE]
Free PMC Article

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