Citations 2
A Genetic Risk Score to Personalize Prostate Cancer Screening, Applied to Population Data
Huynh‐Le, Minh‐Phuong , Fan, Chun Chieh , Karunamuni, Roshan , Walsh, Eleanor , Turner, Emma L. , Gillatt, David , Martin, Richard M. , Neal, David E. , Donovan, Jenny , Parsons, J. Kellogg , Eeles, Rosalind A. , Easton, Douglas F. , Kote‐Jarai, Zsofia , Olama, Ali Amin Al , Garcia, Sara Benlloch, Grönberg, Henrik , Schleutker, Johanna , Tammela, Teuvo L.J. , Nordestgaard, Børge G. , Travis, Ruth C. , Pashayan, Nora , Thibodeau, Stephen N. , Schaid, Daniel J. , Maier, Christiane, Vogel, Walther , Luedeke, Manuel, Herkommer, Kathleen , Kibel, Adam S. , Wokołorczyk, Dominika , Kluźniak, Wojciech , Holleczek, Bernd , Sellers, Thomas A. , Slavov, Chavdar Kroumov, Kaneva, Radka , Mitev, Vanio , Batra, Jyotsna , Teixeira, Manuel R. , Paulo, Paula , Maia, Sofia , Pandha, Hardev , Mills, Ian G. , Dale, Anders M. , Seibert, Tyler M. , Lane, J. Athene , Walsh, Eleanor I , Lane, J Athene , Donovan, Jenny L , Eeles, Rosalind A , Amin Al Olama, Ali , Muir, Kenneth , Grönberg, Henrik , Wiklund, Fredrik E. , Schleutker, Johanna , Key, Tim , Travis, Ruth C , Pharoah, Paul D P , Pashayan, Nora , Herkommer, Kathleen , Cannon-Albright, Lisa A , Brenner, Hermann , Schöttker, Ben , Park, Jong Y , Lin, Hui-Yi , Spurdle, Amanda B , Teixeira, Manuel R , Michael, Agnieszka , Mills, Ian G , Seibert, Tyler M , Dale, Anders M , Martin, Richard M , Batra, Jyotsna , Hamdy, Freddie C. , Muir, Kenneth , Aly, Markus , Sipeky, Csilla , Pharoah, Paul D.P. , Khaw, Kay‐Tee , McDonnell, Shannon K. , Cybulski, Cezary , Cannon‐Albright, Lisa , Park, Jong Y. , Lin, Hui‐Yi , Clements, Judith A. , Spurdle, Amanda B. , Michael, Agnieszka , Andreassen, Ole A.
Cancer Epidemiology, Biomarkers & Prevention | June 24, 2020 | Volume: 29 | Issue: 9 | Pages: 1731-1738
Abstract Background: A polygenic hazard score (PHS), the weighted sum of 54 SNP genotypes, was previously validated for association with clinically significant prostate cancer and for improved prostate cancer screening accuracy. Here, we assess the potential impact of PHS-informed screening. Methods: United Kingdom population incidence data (Cancer Research United Kingdom) and data from the Cluster Randomized Trial of PSA Testing for Prostate Cancer were combined to estimate age-specific clinically significant prostate cancer incidence (Gleason score ≥7, stage T3–T4, PSA ≥10, or nodal/distant metastases). Using HRs estimated from the ProtecT prostate cancer trial, age-specific incidence rates were calculated for various PHS risk percentiles. Risk-equivalent age, when someone with a given PHS percentile has prostate cancer risk equivalent to an average 50-year-old man (50-year-standard risk), was derived from PHS and incidence data. Positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was calculated using PHS-adjusted age groups. Results: The expected age at diagnosis of clinically significant prostate cancer differs by 19 years between the 1st and 99th PHS percentiles: men with PHS in the 1st and 99th percentiles reach the 50-year-standard risk level at ages 60 and 41, respectively. PPV of PSA was higher for men with higher PHS-adjusted age. Conclusions: PHS provides individualized estimates of risk-equivalent age for clinically significant prostate cancer. Screening initiation could be adjusted by a man's PHS. Impact: Personalized genetic risk assessments could inform prostate cancer screening decisions.
Genome-Wide Association Study of Prostate Cancer–Specific Survival
Szulkin, Robert , Whitington, Thomas, Aly, Markus , Grönberg, Henrik , Eeles, Rosalind A. , Easton, Douglas F. , Olama, Ali Amin Al , Benlloch, Sara, Muir, Kenneth , Giles, Graham G. , Southey, Melissa C. , FitzGerald, Liesel M. , Henderson, Brian E., Schumacher, Fredrick R. , Haiman, Christopher A. , Sipeky, Csilla , Tammela, Teuvo L.J. , Nordestgaard, Børge G. , Travis, Ruth C. , Neal, David E. , Donovan, Jenny , Hamdy, Freddie C. , Pashayan, Nora , Stanford, Janet L. , Thibodeau, Stephen N. , McDonnell, Shannon K. , Schaid, Daniel J. , Maier, Christiane, Vogel, Walther , Luedeke, Manuel, Herkommer, Kathleen , Kibel, Adam S. , Lubiński, Jan , Kluźniak, Wojciech , Cannon‐Albright, Lisa , Brenner, Hermann , Herrmann, Volker, Holleczek, Bernd , Sellers, Thomas A. , Lim, Hui-Yi, Kaneva, Radka , Mitev, Vanio , Teixeira, Manuel R. , Paulo, Paula , Maia, Sofia , Pandha, Hardev , Michael, Agnieszka , Batra, Jyotsna , Clements, Judith A. , BioResource, on behalf of the Australian Prostate Cancer, Albanes, Demetrius, Andriole, Gerald L. , Berndt, Sonja I., Gapstur, Susan M. , Giovannucci, Edward L. , Ma, Jing , Mondul, Alison M. , Stampfer, Meir J. , Stevens, Victoria L. , Weinstein, Stephanie J. , Trichopoulou, Antonia , Bueno-de-Mesquita, Bas H., Tjønneland, Anne , Cox, David G. , Mæhle, Lovise, Schleutker, Johanna , Lindström, Sara , Karlsson, Robert , Kote‐Jarai, Zsofia , Key, Tim , Pharoah, Paul D.P. , Khaw, Kay‐Tee , Cybulski, Cezary , Park, Jong Y. , Slavov, Chavdar , Spurdle, Amanda B. , Kierzek, Andrzej , BioResource, on behalf of the Australian Prostate Cancer, Berndt, Sonja I. , Chanock, Stephen Jacob , Hunter, David J. , Kraft, Peter , Marchand, Loı̈c Le , Penney, Kathryn , Wiklund, Fredrik E. , Giles, Graham G , Teixeira, Manuel R , Eeles, Rosalind A , Southey, Melissa C , Tjønneland, Anne , Donovan, Jenny L , Muir, Kenneth , Schleutker, Johanna , Travis, Ruth C , Pashayan, Nora , Cannon-Albright, Lisa A , Michael, Agnieszka , Brenner, Hermann , Batra, Jyotsna , Clements, Judith , Lubinski, Jan , McDonnell, Shannon K
Cancer Epidemiology, Biomarkers & Prevention | August 25, 2015 | Volume: 24 | Issue: 11 | Pages: 1796-1800
Abstract Background: Unnecessary intervention and overtreatment of indolent disease are common challenges in clinical management of prostate cancer. Improved tools to distinguish lethal from indolent disease are critical. Methods: We performed a genome-wide survival analysis of cause-specific death in 24,023 prostate cancer patients (3,513 disease-specific deaths) from the PRACTICAL and BPC3 consortia. Top findings were assessed for replication in a Norwegian cohort (CONOR). Results: We observed no significant association between genetic variants and prostate cancer survival. Conclusions: Common genetic variants with large impact on prostate cancer survival were not observed in this study. Impact: Future studies should be designed for identification of rare variants with large effect sizes or common variants with small effect sizes. Cancer Epidemiol Biomarkers Prev; 24(11); 1796–800. ©2015 AACR.