مورد إلكتروني
Additional SNPs improve risk stratification of a polygenic hazard score for prostate cancer.
| العنوان: | Additional SNPs improve risk stratification of a polygenic hazard score for prostate cancer. |
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| المؤلفون: | Karunamuni, Roshan A |
| المصدر: | Prostate cancer and prostatic diseases; vol 24, iss 2, 532-541; 1365-7852 |
| بيانات النشر: | eScholarship, University of California 2021-06-01 |
| تفاصيل مُضافة: | Karunamuni, Roshan A Huynh-Le, Minh-Phuong Fan, Chun C Thompson, Wesley Eeles, Rosalind A Kote-Jarai, Zsofia Muir, Kenneth Lophatananon, Artitaya UKGPCS collaborators Schleutker, Johanna Pashayan, Nora Batra, Jyotsna APCB BioResource (Australian Prostate Cancer BioResource) Grönberg, Henrik Walsh, Eleanor I Turner, Emma L Lane, Athene Martin, Richard M Neal, David E Donovan, Jenny L Hamdy, Freddie C Nordestgaard, Børge G Tangen, Catherine M MacInnis, Robert J Wolk, Alicja Albanes, Demetrius Haiman, Christopher A Travis, Ruth C Stanford, Janet L Mucci, Lorelei A West, Catharine ML Nielsen, Sune F Kibel, Adam S Wiklund, Fredrik Cussenot, Olivier Berndt, Sonja I Koutros, Stella Sørensen, Karina Dalsgaard Cybulski, Cezary Grindedal, Eli Marie Park, Jong Y Ingles, Sue A Maier, Christiane Hamilton, Robert J Rosenstein, Barry S Vega, Ana IMPACT Study Steering Committee and Collaborators Kogevinas, Manolis Penney, Kathryn L Teixeira, Manuel R Brenner, Hermann John, Esther M Kaneva, Radka Logothetis, Christopher J Neuhausen, Susan L Razack, Azad Newcomb, Lisa F Canary PASS Investigators Gamulin, Marija Usmani, Nawaid Claessens, Frank Gago-Dominguez, Manuela Townsend, Paul A Roobol, Monique J Zheng, Wei Profile Study Steering Committee Mills, Ian G Andreassen, Ole A Dale, Anders M Seibert, Tyler M PRACTICAL Consortium |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | BackgroundPolygenic hazard scores (PHS) can identify individuals with increased risk of prostate cancer. We estimated the benefit of additional SNPs on performance of a previously validated PHS (PHS46).Materials and method180 SNPs, shown to be previously associated with prostate cancer, were used to develop a PHS model in men with European ancestry. A machine-learning approach, LASSO-regularized Cox regression, was used to select SNPs and to estimate their coefficients in the training set (75,596 men). Performance of the resulting model was evaluated in the testing/validation set (6,411 men) with two metrics: (1) hazard ratios (HRs) and (2) positive predictive value (PPV) of prostate-specific antigen (PSA) testing. HRs were estimated between individuals with PHS in the top 5% to those in the middle 40% (HR95/50), top 20% to bottom 20% (HR80/20), and bottom 20% to middle 40% (HR20/50). PPV was calculated for the top 20% (PPV80) and top 5% (PPV95) of PHS as the fraction of individuals with elevated PSA that were diagnosed with clinically significant prostate cancer on biopsy.Results166 SNPs had non-zero coefficients in the Cox model (PHS166). All HR metrics showed significant improvements for PHS166 compared to PHS46: HR95/50 increased from 3.72 to 5.09, HR80/20 increased from 6.12 to 9.45, and HR20/50 decreased from 0.41 to 0.34. By contrast, no significant differences were observed in PPV of PSA testing for clinically significant prostate cancer.ConclusionsIncorporating 120 additional SNPs (PHS166 vs PHS46) significantly improved HRs for prostate cancer, while PPV of PSA testing remained the same. |
| مصطلحات الفهرس: | UKGPCS collaborators, APCB BioResource, IMPACT Study Steering Committee and Collaborators, Canary PASS Investigators, Profile Study Steering Committee, PRACTICAL Consortium, Humans, Prostatic Neoplasms, Prognosis, Models, Statistical, Risk Assessment, Risk Factors, Follow-Up Studies, Predictive Value of Tests, Polymorphism, Single Nucleotide, Adult, Aged, Middle Aged, Male, Biomarkers, Tumor, Aging, Cancer, Prevention, Prostate Cancer, Urologic Diseases, Oncology and Carcinogenesis, Urology & Nephrology, article |
| URL: | |
| الإتاحة: | Open access content. Open access content public |
| ملاحظة: | application/pdf Prostate cancer and prostatic diseases vol 24, iss 2, 532-541 1365-7852 |
| أرقام أخرى: | CDLER oai:escholarship.org:ark:/13030/qt8mn2q2cr qt8mn2q2cr https://escholarship.org/uc/item/8mn2q2crTest https://escholarship.orgTest/ 1367379046 |
| المصدر المساهم: | UC MASS DIGITIZATION From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.on1367379046 |
| قاعدة البيانات: | OAIster |
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