| Title: |
Additional SNPs improve risk stratification of a polygenic hazard score for prostate cancer |
| Authors: |
Karunamuni, Roshan A.; Huynh-Le, Minh-Phuong; Fan, Chun C.; Thompson, Wesley; Eeles, Rosalind A.; Kote-Jarai, Zsofia; Muir, Kenneth; Lophatananon, Artitaya; Schleutker, Johanna; Pashayan, Nora; Batra, Jyotsna; Groenberg, Henrik; Walsh, Eleanor I.; Turner, Emma L.; Lane, Athene; Martin, Richard M.; Neal, David E.; Donovan, Jenny L.; Hamdy, Freddie C.; Nordestgaard, Borge 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 M.L.; Nielsen, Sune F.; Kibel, Adam S.; Wiklund, Fredrik; Cussenot, Olivier; Berndt, Sonja I.; Koutros, Stella; Sorensen, Karina Dalsgaard; Cybulski, Cezary; Grindedal, Eli Marie; Park, Jong Y.; Ingles, Sue A.; Maier, Christiane; Hamilton, Robert J.; Rosenstein, Barry S.; Vega, Ana; 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.; Gamulin, Marija; Usmani, Nawaid; Claessens, Frank; Gago-Dominguez, Manuela; Townsend, Paul A.; Roobol, Monique J.; Zheng, Wei; Mills, Ian G.; Andreassen, Ole A.; Dale, Anders M.; Seibert, Tyler M. |
| Source: |
ISSN:1365-7852 ; ISSN:1476-5608 ; Prostate Cancer And Prostatic Diseases, vol. 24 (2), (532-541. |
| Publisher Information: |
Springer Nature [academic journals on nature.com] |
| Publication Year: |
2021 |
| Subject Terms: |
Science & Technology; Life Sciences & Biomedicine; Oncology; Urology & Nephrology; SUSCEPTIBILITY; Adult; Aged; Biomarkers; Tumor; Follow-Up Studies; Humans; Male; Middle Aged; Models; Statistical; Polymorphism; Single Nucleotide; Predictive Value of Tests; Prognosis; Prostatic Neoplasms; Risk Assessment; Risk Factors; UKGPCS collaborators; APCB BioResource (Australian Prostate Cancer BioResource); IMPACT Study Steering Committee and Collaborators; Canary PASS Investigators; Profile Study Steering Committee; PRACTICAL Consortium; 1112 Oncology and Carcinogenesis; 3202 Clinical sciences |
| Description: |
BACKGROUND: Polygenic 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 METHOD: 180 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. RESULTS: 166 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. CONCLUSIONS: Incorporating 120 additional SNPs (PHS166 vs PHS46) significantly improved HRs for prostate cancer, while PPV of PSA testing remained the same. ; sponsorship: This study was funded in part by a grant from the United States National Institute of Health/National Institute of Biomedical Imaging and Bioengineering (#K08EB026503), the University of California Cancer Research Coordinating Committee (#C21CR2060), the Research Council of Norway (#223273), KG Jebsen Stiftelsen, and South East Norway Health Authority. (United States National Institute of ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/octet-stream |
| Language: |
English |
| Relation: |
https://lirias.kuleuven.be/handle/123456789/676675; https://pubmed.ncbi.nlm.nih.gov/33420416 |
| DOI: |
10.1038/s41391-020-00311-2 |
| Availability: |
https://lirias.kuleuven.be/handle/123456789/676675; https://lirias.kuleuven.be/retrieve/6744ae0b-c0fd-46bf-9cbb-99cc0ff2394f; https://doi.org/10.1038/s41391-020-00311-2; https://pubmed.ncbi.nlm.nih.gov/33420416 |
| Rights: |
info:eu-repo/semantics/openAccess ; public |
| Accession Number: |
edsbas.C906395A |
| Database: |
BASE |