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Prostate cancer riskstratificationimprovement acrossmultiple ancestrieswith new polygenichazard score Minh‐Phuong Huynh‐LeRoshan KarunamuniChun Chieh Fan2022 год

Prostate cancer risk stratification improvement across multiple ancestries with new polygenic hazard score
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Аннотация: 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.
Год издания: 2022
Авторы: Minh‐Phuong Huynh‐Le, Roshan Karunamuni, Chun Chieh Fan, Asona Lui, Wesley K. Thompson, Marı́a Elena Martı́nez, Rosalind A. Eeles, Zsofia Kote‐Jarai, Kenneth Muir, Artitaya Lophatananon, Johanna Schleutker, Nora Pashayan, Jyotsna Batra, Henrik Grönberg, David E. Neal, Børge G. Nordestgaard, Catherine M. Tangen, Robert J. MacInnis, Alicja Wolk, Demetrius Albanes, Christopher A. Haiman, Ruth C. Travis, William J. Blot, Janet L. Stanford, Lorelei A. Mucci, Catharine West, Sune F. Nielsen, Adam S. Kibel, Olivier Cussenot, Sonja Berndt, Stella Koutros, Karina D. Sørensen, Cezary Cybulski, Eli Marie Grindedal, F. Ménégaux, Jong Y. Park, Sue A. Ingles, Christiane Maier, Robert J. Hamilton, Barry S. Rosenstein, Yong‐Jie Lu, Stephen Watya, Ana Vega, Manolis Kogevinas, Fredrik Wiklund, Kathryn L. Penney, Chad Huff, Manuel R. Teixeira, Luc Multigner, Robin J. Leach, Hermann Brenner, Esther M. John, Radka Kaneva, Christopher J. Logothetis, Susan L. Neuhausen, Kim De Ruyck, Piet Ost, Azad Hassan Abdul Razack, Lisa F. Newcomb, Jay H. Fowke, Marija Gamulin, Aswin Abraham, Frank Claessens, Jose E. Castelao, Paul A. Townsend, Dana C. Crawford, György Petrovics, Ron H. N. van Schaik, Marie‐Élise Parent, Jennifer J. Hu, Wei Zheng, Ian G. Mills, Ole A. Andreassen, Anders M. Dale, Tyler M. Seibert
Издательство: Springer Nature
Источник: Prostate Cancer and Prostatic Diseases
Ключевые слова: Prostate Cancer Diagnosis and Treatment, Prostate Cancer Treatment and Research, Genetic Associations and Epidemiology
Другие ссылки: Prostate Cancer and Prostatic Diseases (PDF)
Prostate Cancer and Prostatic Diseases (HTML)
univ-rennes.hal.science (HTML)
PubMed Central (HTML)
PubMed (HTML)