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Br J Cancer. 2015 Sep 29;113(7):1086-93. doi: 10.1038/bjc.2015.289. Epub 2015 Aug 20.

Reducing overdiagnosis by polygenic risk-stratified screening: findings from the Finnish section of the ERSPC.

Author information

1
Department of Applied Health Research, University College London, 1-19 Torrington Place, London WC1E 7HB, UK.
2
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge CB1 8RN, UK.
3
Department of Medical Biochemistry and Genetics, University of Turku, Turku FI20014, Finland.
4
Finnish Cancer Registry, Helsinki FI 00130, Finland.
5
Department of Surgery, Tampere University Hospital and School of Medicine, University of Tampere, Tampere FI 33014, Finland.
6
Division of Genetics and Epidemiology, The Institute of Cancer Research & Royal Marsden NHS Foundation Trust, London SM2 5NG, UK.
7
Centre for Cancer Prevention, Mathematics and Statistics, Wolfson Institute of Preventive Medicine, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
8
School of Health Sciences, University of Tampere, Tampere FI 33014, Finland.

Abstract

BACKGROUND:

We derived estimates of overdiagnosis by polygenic risk groups and examined whether polygenic risk-stratified screening for prostate cancer reduces overdiagnosis.

METHODS:

We calculated the polygenic risk score based on genotypes of 66 known prostate cancer loci for 4967 men from the Finnish section of the European Randomised Study of Screening for Prostate Cancer. We stratified the 72 072 men in the trial into those with polygenic risk below and above the median. Using a maximum likelihood method based on interval cancers, we estimated the mean sojourn time (MST) and episode sensitivity. For each polygenic risk group, we estimated the proportion of screen-detected cancers that are likely to be overdiagnosed from the difference between the observed and expected number of screen-detected cancers.

RESULTS:

Of the prostate cancers, 74% occurred among men with polygenic risk above population median. The sensitivity was 0.55 (95% confidence interval (CI) 0.45-0.65) and MST 6.3 (95% CI 4.2-8.3) years. The overall overdiagnosis was 42% (95% CI 37-52) of the screen-detected cancers, with 58% (95% CI 54-65) in men with the lower and 37% (95% CI 31-47) in those with higher polygenic risk.

CONCLUSION:

Targeting screening to men at higher polygenic risk could reduce the proportion of cancers overdiagnosed.

PMID:
26291059
PMCID:
PMC4651137
DOI:
10.1038/bjc.2015.289
[Indexed for MEDLINE]
Free PMC Article

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