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- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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- Conti, David, V, et al.
(författare)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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- Tarrío, Diego, et al.
(författare)
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Measurement of the angular distribution of fission fragments using a PPAC assembly at CERN n_TOF
- 2014
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 743, s. 79-85
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Tidskriftsartikel (refereegranskat)abstract
- A fission reaction chamber based on Parallel Plate Avalanche Counters (PPACs) was built for measuring angular distributions of fragments emitted in neutron-induced fission of actinides at the neutron beam available at the Neutron Time-Of-Flight (n_TOF) facility at CERN. The detectors and the samples were tilted 45 degrees with respect to the neutron beam direction to cover all the possible values of the emission angle of the fission fragments. The main features of this setup are discussed and results on the fission fragment angular distribution are provided for the Th-232(n,f) reaction around the fission threshold. The results are compared with the available data in the literature, demonstrating the good capabilities of this setup.
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- Tarrío, Diego, et al.
(författare)
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Neutron-induced fission cross sections of Th-232 and U-233 up to 1 GeV using parallel plate avalanche counters at the CERN n_TOF facility
- 2023
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Ingår i: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 107:4
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Tidskriftsartikel (refereegranskat)abstract
- The neutron-induced fission cross sections of Th-232 and U-233 were measured relative to U-235 in a wide neutron energy range up to 1 GeV (and from fission threshold in the case of Th-232, and from 0.7 eV in case of U-233), using the white-spectrum neutron source at the CERN Neutron Time-of-Flight (n_TOF) facility. Parallel plate avalanche counters (PPACs) were used, installed at the Experimental Area 1 (EAR1), which is located at 185 m from the neutron spallation target. The anisotropic emission of fission fragments were taken into account in the detection efficiency by using, in the case of U-233, previous results available in EXFOR, whereas in the case of Th-232 these data were obtained from our measurement, using PPACs and targets tilted 45 degrees with respect to the neutron beam direction. Finally, the obtained results are compared with past measurements and major evaluated nuclear data libraries. Calculations using the high-energy reaction models INCL++ and ABLA07 were performed and some of their parameters were modified to reproduce the experimental results. At high energies, where no other neutron data exist, our results are compared with experimental data on proton-induced fission. Moreover, the dependence of the fission cross section at 1 GeV with the fissility parameter of the target nucleus is studied by combining those ( p, f) data with our (n, f) data on Th-232 and U-233 and on other isotopes studied earlier at n_TOF using the same experimental setup.
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- Dadaev, T, et al.
(författare)
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Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2256-
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling.
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