Citations 2
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.
Multiple Novel Prostate Cancer Predisposition Loci Confirmed by an International Study: The PRACTICAL Consortium
Easton, Douglas F. , Stanford, Janet L. , Ostrander, Elaine A. , Schleutker, Johanna , Schaid, Daniel J. , Thibodeau, Stephen N. , Dörk, Thilo , Neal, David E. , Cox, Angela , Maier, Christiane, Guy, Michelle, Lophatananon, Artitaya, Kedda, Mary-Anne, Spurdle, Amanda B. , Steginga, Suzanne K., John, Esther M. , Giles, Graham G. , Chappuis, Pierre O. , Hutter, Pierre, Foulkes, William D. , Hamel, Nancy , Salinas, Claudia A., Karyadi, Danielle M. , Johanneson, Bo, Wahlfors, Tiina , Tammela, Teuvo L.J. , Corral, Román, McDonnell, Shannon K. , Schürmann, Peter , Meyer, Andreas , Kuefer, Rainer, Leongamornlert, Daniel , Tymrakiewicz, Malgorzata, Liu, Jo‐Fen , O’Mara, Tracy A. , Gardiner, Robert A. , Aitken, Joanne F. , Joshi, Amit D. , Severi, Gianluca , English, Dallas R. , Southey, Melissa C. , Edwards, Stephen M., Olama, Ali Amin Al , Eeles, Rosalind A. , Donovan, Jenny , Chambers, Suzanne K. , Kote‐Jarai, Zsofia , Ingles, Sue A. , Vogel, W. , Muir, Kenneth , Hopper, John L. , Koopmeiners, Joseph Stephen , Stern, Mariana Carla , Dörk, Thilo , Giles, Graham G , Spurdle, Amanda B , Foulkes, William D , Eeles, Rosalind A , John, Esther M , Southey, Melissa C , English, Dallas R , Donovan, Jenny L , Schleutker, Johanna , O'Mara, Tracy A , Cox, Angela , Severi, Gianluca , McDonnell, Shannon K
Cancer Epidemiology, Biomarkers & Prevention | August 15, 2008 | Volume: 17 | Issue: 8 | Pages: 2052-2061
Abstract A recent genome-wide association study found that genetic variants on chromosomes 3, 6, 7, 10, 11, 19 and X were associated with prostate cancer risk. We evaluated the most significant single-nucleotide polymorphisms (SNP) in these loci using a worldwide consortium of 13 groups (PRACTICAL). Blood DNA from 7,370 prostate cancer cases and 5,742 male controls was analyzed by genotyping assays. Odds ratios (OR) associated with each genotype were estimated using unconditional logistic regression. Six of the seven SNPs showed clear evidence of association with prostate cancer (P = 0.0007-P = 10−17). For each of these six SNPs, the estimated per-allele OR was similar to those previously reported and ranged from 1.12 to 1.29. One SNP on 3p12 (rs2660753) showed a weaker association than previously reported [per-allele OR, 1.08 (95% confidence interval, 1.00-1.16; P = 0.06) versus 1.18 (95% confidence interval, 1.06-1.31)]. The combined risks associated with each pair of SNPs were consistent with a multiplicative risk model. Under this model, and in combination with previously reported SNPs on 8q and 17q, these loci explain 16% of the familial risk of the disease, and men in the top 10% of the risk distribution have a 2.1-fold increased risk relative to general population rates. This study provides strong confirmation of these susceptibility loci in multiple populations and shows that they make an important contribution to prostate cancer risk prediction. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2052–61)