Huynh-Le, Minh-Phuong and Karunamuni, Roshan and Fan, Chun Chieh and Asona, Lui and Thompson, Wesley K. and Martinez, Maria Elena and Eeles, Rosalind A. and Kote-Jarai, Zsofia and Muir, Kenneth R. and Lophatananon, Artitaya and Schleutker, Johanna and Pashayan, Nora and Batra, Jyotsna and Groenberg, Henrik and Neal, David E. and Nordestgaard, Borge G. and Tangen, Catherine M. and MacInnis, Robert J. and Wolk, Alicja and Albanes, Demetrius and Haiman, Christopher A. and Travis, Ruth C. and Blot, William J. and Stanford, Janet L. and Mucci, Lorelei A. and West, Catharine M. L. and Nielsen, Sune F. and Kibel, Adam S. and Cussenot, Olivier and Berndt, Sonja and Koutros, Stella and Sorensen, Karina Dalsgaard and Cybulski, Cezary and Grindedal, Eli Marie and Menegaux, Florence and Park, Jong Y. and Ingles, Sue A. and Maier, Christiane and Hamilton, Robert J. and Rosenstein, Barry S. and Lu, Yong-Jie and Watya, Stephen and Vega, Ana and Kogevinas, Manolis and Wiklund, Fredrik and Penney, Kathryn L. and Huff, Chad D. and Teixeira, Manuel R. and Multigner, Luc and Leach, Robin J. and Brenner, Hermann and John, Esther M. and Kaneva, Radka and Logothetis, Christopher J. and Neuhausen, Susan L. and De Ruyck, Kim and Ost, Piet and Razack, Azad Hassan Abdul and Newcomb, Lisa F. and Fowke, Jay H. and Gamulin, Marija and Abraham, Aswin and Claessens, Frank and Castelao, Jose Esteban and Townsend, Paul A. and Crawford, Dana C. and Petrovics, Gyorgy and van Schaik, Ron H. N. and Parent, Marie-Elise and Hu, Jennifer J. and Zheng, Wei and Mills, Ian G. and Andreassen, Ole A. and Dale, Anders M. and Seibert, Tyler M. (2022) Prostate cancer risk stratification improvement across multiple ancestries with new polygenic hazard score. Prostate Cancer and Prostatic Diseases, 25 (4). pp. 755-761. ISSN 1365-7852, DOI https://doi.org/10.1038/s41391-022-00497-7.
Full text not available from this repository.Abstract
Background Prostate cancer risk stratification using single-nucleotide polymorphisms (SNPs) demonstrates considerable promise in men of European, Asian, and African genetic ancestries, but there is still need for increased accuracy. We evaluated whether including additional SNPs in a prostate cancer polygenic hazard score (PHS) would improve associations with clinically significant prostate cancer in multi-ancestry datasets. Methods In total, 299 SNPs previously associated with prostate cancer were evaluated for inclusion in a new PHS, using a LASSO-regularized Cox proportional hazards model in a training dataset of 72,181 men from the PRACTICAL Consortium. The PHS model was evaluated in four testing datasets: African ancestry, Asian ancestry, and two of European Ancestry-the Cohort of Swedish Men (COSM) and the ProtecT study. Hazard ratios (HRs) were estimated to compare men with high versus low PHS for association with clinically significant, with any, and with fatal prostate cancer. The impact of genetic risk stratification on the positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was also measured. Results The final model (PHS290) had 290 SNPs with non-zero coefficients. Comparing, for example, the highest and lowest quintiles of PHS290, the hazard ratios (HRs) for clinically significant prostate cancer were 13.73 95% CI: 12.43-15.16] in ProtecT, 7.07 6.58-7.60] in African ancestry, 10.31 9.58-11.11] in Asian ancestry, and 11.18 10.34-12.09] in COSM. Similar results were seen for association with any and fatal prostate cancer. Without PHS stratification, the PPV of PSA testing for clinically significant prostate cancer in ProtecT was 0.12 (0.11-0.14). For the top 20% and top 5% of PHS290, the PPV of PSA testing was 0.19 (0.15-0.22) and 0.26 (0.19-0.33), respectively. Conclusions We demonstrate better genetic risk stratification for clinically significant prostate cancer than prior versions of PHS in multi-ancestry datasets. This is promising for implementing precision-medicine approaches to prostate cancer screening decisions in diverse populations.
| Item Type: | Article |
|---|---|
| Funders: | University of California System [C21CR2060], United States National Institute of Health/National Institute of Biomedical Imaging and Bioengineering [K08EB026503], Prostate Cancer Foundation, Research Council of Norway [223273], KG Jebsen Stiftelsen, South East Norway Health Authority, United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI) [UG1CA189974], United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Biomedical Imaging & Bioengineering (NIBIB) [K08EB026503] |
| Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
| Divisions: | Faculty of Medicine > Surgery Department |
| Depositing User: | Ms Koh Ai Peng |
| Date Deposited: | 19 Jul 2024 08:51 |
| Last Modified: | 19 Jul 2024 08:51 |
| URI: | http://eprints.um.edu.my/id/eprint/46285 |
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