Citations 14
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.
Prediction of individual genetic risk to prostate cancer using a polygenic score
Szulkin, Robert , Whitington, Thomas, Aly, Markus , 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. , Schleutker, Johanna , 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 , Butterbach, Katja, Stegmaier, Christa, Sellers, Thomas A. , Lim, Hui-Yi, Kaneva, Radka , Mitev, Vanio , Batra, Jyotsna , Clements, Judith A. , BioResource, The Australian Prostate Cancer, Teixeira, Manuel R. , Maia, Sofia , Pandha, Hardev, Michael, Agnieszka , Kierzek, Andrzej , Grönberg, Henrik , Karyadi, Danielle M. , Horvath, Lisa G. , Weischer, Maren , Saunders, Edward J. , Eklund, Martin , Kote‐Jarai, Zsofia , Wahlfors, Tiina , Key, Tim , Pharoah, Paul D.P. , Khaw, Kay‐Tee , Cybulski, Cezary , Park, Jong Y. , Slavov, Chavdar , Spurdle, Amanda B. , Paulo, Paula Loureiro , Wiklund, Fredrik E. , Paulo, Paula , Giles, Graham G , Teixeira, Manuel R , Eeles, Rosalind A , Southey, Melissa C , 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
The Prostate | July 14, 2015 | Volume: 75 | Issue: 13 | Pages: 1467-1474
Risk Analysis of Prostate Cancer in PRACTICAL, a Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci
Olama, Ali Amin Al , Benlloch, Sara, Antoniou, Antonis C. , Giles, Graham G. , Severi, Gianluca , Neal, David E. , Hamdy, Freddie C. , Donovan, Jenny , Muir, Kenneth , Schleutker, Johanna , Henderson, Brian E., Haiman, Christopher A. , Schumacher, Fredrick R. , Pashayan, Nora , Ostrander, Elaine A. , Stanford, Janet L. , Batra, Jyotsna , Clements, Judith A. , Chambers, Suzanne K. , Weischer, Maren , Nordestgaard, Børge G. , Sørensen, Karina D. , Ørntoft, Torben F., Maier, Christiane, Doerk, Thilo, Dickinson, Joanne L. , Cannon‐Albright, Lisa , Brenner, Hermann , Habuchi, Tomonori , Thibodeau, Stephen N. , Cooney, Kathleen A. , Chappuis, Pierre O. , Hutter, Pierre, Kaneva, Radka , Foulkes, William D. , Lu, Yong‐Jie , Zhang, Hongwei , Stephenson, Robert A., Cox, Angela , Southey, Melissa C. , FitzGerald, Liesel M. , Leongamornlert, Daniel , Saunders, Edward J. , Tymrakiewicz, Malgorzata, Guy, Michelle, Little, Sarah J., Govindasami, Koveela, Sawyer, Emma, Wilkinson, Rosemary, Herkommer, Kathleen , Hopper, John L. , Lophatonanon, Aritaya, Rinckleb, Antje E., Eeles, Rosalind A. , Easton, Douglas F. , Dörk, Thilo , Aitken, Joanne F. , Borre, Michael , Lose, Felicity , Srinivasan, Srilakshmi , Tilley, Wayne D. , Samaratunga, Hemamali , Goranova, Teodora , Catto, James W.F. , Pharoah, Paul D.P. , Ingles, Sue A. , Park, Jong Y. , Cybulski, Cezary , Rebbeck, Timothy R. , Zeigler-Johnson, Charnita M , Zeegers, Maurice Petrus , Spurdle, Amanda B. , Dadaev, Tokhir , Kote‐Jarai, Zsofia , Dwyer, Terry , Dörk, Thilo , Giles, Graham G , Foulkes, William D , Eeles, Rosalind A , Southey, Melissa C , Donovan, Jenny L , Muir, Kenneth , Schleutker, Johanna , Pashayan, Nora , Cannon-Albright, Lisa A , Brenner, Hermann , Cox, Angela , Samaratunga, Hemamali , Severi, Gianluca , Batra, Jyotsna , Clements, Judith
Cancer Epidemiology, Biomarkers & Prevention | April 3, 2015 | Volume: 24 | Issue: 7 | Pages: 1121-1129
Abstract Background: Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer. Methods: We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS). We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived age-specific absolute risks of developing prostate cancer by PRS stratum and family history. Results: The prostate cancer risk for men in the top 1% of the PRS distribution was 30.6 (95% CI, 16.4–57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI, 3.2–5.5) fold compared with the median risk. The absolute risk of prostate cancer by age of 85 years was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation = 0.09). Conclusions: Risk profiling can identify men at substantially increased or reduced risk of prostate cancer. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of prostate cancer. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles. Impact: We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs. Cancer Epidemiol Biomarkers Prev; 24(7); 1121–9. ©2015 AACR.
A Large-Scale Analysis of Genetic Variants within Putative miRNA Binding Sites in Prostate Cancer
Stegeman, Shane, Amankwah, Ernest K. , Klein, Kerenaftali, Kim, Donghwa , Lin, Hui‐Yi , Permuth‐Wey, Jennifer, Sellers, Thomas A. , Srinivasan, Srilakshmi , Eeles, Rosalind A. , Easton, Doug , Olama, Ali Amin Al , Benlloch, Sara, Muir, Kenneth , Wiklund, Fredrik, Grönberg, Henrik , Haiman, Christopher A. , Schleutker, Johanna , Nordestgaard, Børge G. , Travis, Ruth C. , Neal, David E. , Stanford, Janet L. , Blot, William J. , Thibodeau, Stephen N. , Maier, Christiane, Kibel, Adam S. , Brenner, Hermann , Kaneva, Radka , Teixeira, Manuel R. , BioResource, Australian Prostate Cancer, Clements, Judith A. , Batra, Jyotsna , Wahlfors, Tiina , Leongamornlert, Daniel , Southey, Melissa C. , Schumacher, Fredrick R. , Henrique, Rui , Hamdy, Freddie C. , Donovan, Jenny , Pashayan, Nora , Weischer, Maren , Saunders, Edward J. , Mitev, Vanio , Maia, Sofia , Tilley, Wayne D. , Thibodeau, Stephen, O’Mara, Tracy A. , Kote‐Jarai, Zsofia , Giles, Graham G. , Pharoah, Paul D.P. , Khaw, Kay‐Tee , Cybulski, Cezary , Cannon‐Albright, Lisa , BioResource, Australian Prostate Cancer, Spurdle, Amanda B. , Park, Jong Y. , Paulo, Paula , Teixeira, Manuel R , Eeles, Rosalind A , Southey, Melissa C , Donovan, Jenny L , Muir, Kenneth , Schleutker, Johanna , Travis, Ruth C , Pashayan, Nora , Lin, Hui-Yi , Brenner, Hermann , Pinto, Pedro , Batra, Jyotsna , Clements, Judith
Cancer Discovery | February 17, 2015 | Volume: 5 | Issue: 4 | Pages: 368-379
Abstract Prostate cancer is the second most common malignancy among men worldwide. Genome-wide association studies have identified 100 risk variants for prostate cancer, which can explain approximately 33% of the familial risk of the disease. We hypothesized that a comprehensive analysis of genetic variations found within the 3′ untranslated region of genes predicted to affect miRNA binding (miRSNP) can identify additional prostate cancer risk variants. We investigated the association between 2,169 miRSNPs and prostate cancer risk in a large-scale analysis of 22,301 cases and 22,320 controls of European ancestry from 23 participating studies. Twenty-two miRSNPs were associated (P < 2.3 × 10−5) with risk of prostate cancer, 10 of which were within 7 genes previously not mapped by GWAS studies. Further, using miRNA mimics and reporter gene assays, we showed that miR-3162-5p has specific affinity for the KLK3 rs1058205 miRSNP T-allele, whereas miR-370 has greater affinity for the VAMP8 rs1010 miRSNP A-allele, validating their functional role. Significance: Findings from this large association study suggest that a focus on miRSNPs, including functional evaluation, can identify candidate risk loci below currently accepted statistical levels of genome-wide significance. Studies of miRNAs and their interactions with SNPs could provide further insights into the mechanisms of prostate cancer risk. Cancer Discov; 5(4); 368–79. ©2015 AACR. See related commentary by Yousef, p. 351 This article is highlighted in the In This Issue feature, p. 333