TY - JOUR
T1 - Implications of polygenic risk-stratified screening for prostate cancer on overdiagnosis
AU - Pashayan, Nora
AU - Duffy, Stephen W.
AU - Neal, David E.
AU - Hamdy, Freddie C.
AU - Donovan, Jenny L.
AU - Martin, Richard M.
AU - Harrington, Patricia
AU - Benlloch, Sara
AU - Amin Al Olama, Ali
AU - Shah, Mitul
AU - Kote-Jarai, Zsofia
AU - Easton, Douglas F.
AU - Eeles, Rosalind
AU - Pharoah, Paul D.
N1 - Publisher Copyright:
© American College of Medical Genetics and Genomics.
PY - 2015/10/1
Y1 - 2015/10/1
N2 - 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.
AB - 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.
KW - overdiagnosis
KW - polygenic risk
KW - prostate cancer
KW - riskstratified screening
UR - https://www.scopus.com/pages/publications/84942994349
U2 - 10.1038/gim.2014.192
DO - 10.1038/gim.2014.192
M3 - Artículo
C2 - 25569441
AN - SCOPUS:84942994349
SN - 1098-3600
VL - 17
SP - 789
EP - 795
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 10
ER -