domingo, 18 de enero de 2015

Implications of polygenic risk-stratified screening for prostate cancer on overdiagnosis : Genetics in Medicine : Nature Publishing Group

Implications of polygenic risk-stratified screening for prostate cancer on overdiagnosis : Genetics in Medicine : Nature Publishing Group





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

Genetics in Medicine
 
(2014)
 
doi:10.1038/gim.2014.192
Received
 
Accepted
 
Published online 

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.
Genet Med advance online publication 08 January 2015

Keywords:

 
overdiagnosis; polygenic risk; prostate cancer; risk-stratified screening

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