dc.contributor.author | Chen, F | |
dc.contributor.author | Madduri, RK | |
dc.contributor.author | Rodriguez, AA | |
dc.contributor.author | Darst, BF | |
dc.contributor.author | Chou, A | |
dc.contributor.author | Sheng, X | |
dc.contributor.author | Wang, A | |
dc.contributor.author | Shen, J | |
dc.contributor.author | Saunders, EJ | |
dc.contributor.author | Rhie, SK | |
dc.contributor.author | Bensen, JT | |
dc.contributor.author | Ingles, SA | |
dc.contributor.author | Kittles, RA | |
dc.contributor.author | Strom, SS | |
dc.contributor.author | Rybicki, BA | |
dc.contributor.author | Nemesure, B | |
dc.contributor.author | Isaacs, WB | |
dc.contributor.author | Stanford, JL | |
dc.contributor.author | Zheng, W | |
dc.contributor.author | Sanderson, M | |
dc.contributor.author | John, EM | |
dc.contributor.author | Park, JY | |
dc.contributor.author | Xu, J | |
dc.contributor.author | Wang, Y | |
dc.contributor.author | Berndt, SI | |
dc.contributor.author | Huff, CD | |
dc.contributor.author | Yeboah, ED | |
dc.contributor.author | Tettey, Y | |
dc.contributor.author | Lachance, J | |
dc.contributor.author | Tang, W | |
dc.contributor.author | Rentsch, CT | |
dc.contributor.author | Cho, K | |
dc.contributor.author | Mcmahon, BH | |
dc.contributor.author | Biritwum, RB | |
dc.contributor.author | Adjei, AA | |
dc.contributor.author | Tay, E | |
dc.contributor.author | Truelove, A | |
dc.contributor.author | Niwa, S | |
dc.contributor.author | Sellers, TA | |
dc.contributor.author | Yamoah, K | |
dc.contributor.author | Murphy, AB | |
dc.contributor.author | Crawford, DC | |
dc.contributor.author | Patel, AV | |
dc.contributor.author | Bush, WS | |
dc.contributor.author | Aldrich, MC | |
dc.contributor.author | Cussenot, O | |
dc.contributor.author | Petrovics, G | |
dc.contributor.author | Cullen, J | |
dc.contributor.author | Neslund-Dudas, CM | |
dc.contributor.author | Stern, MC | |
dc.contributor.author | Kote-Jarai, Z | |
dc.contributor.author | Govindasami, K | |
dc.contributor.author | Cook, MB | |
dc.contributor.author | Chokkalingam, AP | |
dc.contributor.author | Hsing, AW | |
dc.contributor.author | Goodman, PJ | |
dc.contributor.author | Hoffmann, TJ | |
dc.contributor.author | Drake, BF | |
dc.contributor.author | Hu, JJ | |
dc.contributor.author | Keaton, JM | |
dc.contributor.author | Hellwege, JN | |
dc.contributor.author | Clark, PE | |
dc.contributor.author | Jalloh, M | |
dc.contributor.author | Gueye, SM | |
dc.contributor.author | Niang, L | |
dc.contributor.author | Ogunbiyi, O | |
dc.contributor.author | Idowu, MO | |
dc.contributor.author | Popoola, O | |
dc.contributor.author | Adebiyi, AO | |
dc.contributor.author | Aisuodionoe-Shadrach, OI | |
dc.contributor.author | Ajibola, HO | |
dc.contributor.author | Jamda, MA | |
dc.contributor.author | Oluwole, OP | |
dc.contributor.author | Nwegbu, M | |
dc.contributor.author | Adusei, B | |
dc.contributor.author | Mante, S | |
dc.contributor.author | Darkwa-Abrahams, A | |
dc.contributor.author | Mensah, JE | |
dc.contributor.author | Diop, H | |
dc.contributor.author | Van Den Eeden, SK | |
dc.contributor.author | Blanchet, P | |
dc.contributor.author | Fowke, JH | |
dc.contributor.author | Casey, G | |
dc.contributor.author | Hennis, AJ | |
dc.contributor.author | Lubwama, A | |
dc.contributor.author | Thompson, IM | |
dc.contributor.author | Leach, R | |
dc.contributor.author | Easton, DF | |
dc.contributor.author | Preuss, MH | |
dc.contributor.author | Loos, RJ | |
dc.contributor.author | Gundell, SM | |
dc.contributor.author | Wan, P | |
dc.contributor.author | Mohler, JL | |
dc.contributor.author | Fontham, ET | |
dc.contributor.author | Smith, GJ | |
dc.contributor.author | Taylor, JA | |
dc.contributor.author | Srivastava, S | |
dc.contributor.author | Eeles, RA | |
dc.contributor.author | Carpten, JD | |
dc.contributor.author | Kibel, AS | |
dc.contributor.author | Multigner, L | |
dc.contributor.author | Parent, M-É | |
dc.contributor.author | Menegaux, F | |
dc.contributor.author | Cancel-Tassin, G | |
dc.contributor.author | Klein, EA | |
dc.contributor.author | Andrews, C | |
dc.contributor.author | Rebbeck, TR | |
dc.contributor.author | Brureau, L | |
dc.contributor.author | Ambs, S | |
dc.contributor.author | Edwards, TL | |
dc.contributor.author | Watya, S | |
dc.contributor.author | Chanock, SJ | |
dc.contributor.author | Witte, JS | |
dc.contributor.author | Blot, WJ | |
dc.contributor.author | Michael Gaziano, J | |
dc.contributor.author | Justice, AC | |
dc.contributor.author | Conti, DV | |
dc.contributor.author | Haiman, CA | |
dc.coverage.spatial | Switzerland | |
dc.date.accessioned | 2023-06-06T10:27:27Z | |
dc.date.available | 2023-06-06T10:27:27Z | |
dc.date.issued | 2023-02-27 | |
dc.identifier | S0302-2838(23)02561-7 | |
dc.identifier.citation | European Urology, 2023, pp. S0302-2838(23)02561-7 - | |
dc.identifier.issn | 0302-2838 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5826 | |
dc.identifier.eissn | 1873-7560 | |
dc.identifier.eissn | 1873-7560 | |
dc.identifier.doi | 10.1016/j.eururo.2023.01.022 | |
dc.description.abstract | BACKGROUND: Genetic factors play an important role in prostate cancer (PCa) susceptibility. OBJECTIVE: To discover common genetic variants contributing to the risk of PCa in men of African ancestry. DESIGN, SETTING, AND PARTICIPANTS: We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Common genotyped and imputed variants were tested for their association with PCa risk. Novel susceptibility loci were identified and incorporated into a multiancestry polygenic risk score (PRS). The PRS was evaluated for associations with PCa risk and disease aggressiveness. RESULTS AND LIMITATIONS: Nine novel susceptibility loci for PCa were identified, of which seven were only found or substantially more common in men of African ancestry, including an African-specific stop-gain variant in the prostate-specific gene anoctamin 7 (ANO7). A multiancestry PRS of 278 risk variants conferred strong associations with PCa risk in African ancestry studies (odds ratios [ORs] >3 and >5 for men in the top PRS decile and percentile, respectively). More importantly, compared with men in the 40-60% PRS category, men in the top PRS decile had a significantly higher risk of aggressive PCa (OR = 1.23, 95% confidence interval = 1.10-1.38, p = 4.4 × 10-4). CONCLUSIONS: This study demonstrates the importance of large-scale genetic studies in men of African ancestry for a better understanding of PCa susceptibility in this high-risk population and suggests a potential clinical utility of PRS in differentiating between the risks of developing aggressive and nonaggressive disease in men of African ancestry. PATIENT SUMMARY: In this large genetic study in men of African ancestry, we discovered nine novel prostate cancer (PCa) risk variants. We also showed that a multiancestry polygenic risk score was effective in stratifying PCa risk, and was able to differentiate risk of aggressive and nonaggressive disease. | |
dc.format | Print-Electronic | |
dc.format.extent | S0302-2838(23)02561-7 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER | |
dc.relation.ispartof | European Urology | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject | African ancestry | |
dc.subject | Aggressive prostate cancer | |
dc.subject | Polygenic risk score | |
dc.subject | Prostate cancer | |
dc.subject | Susceptibility loci | |
dc.title | Evidence of Novel Susceptibility Variants for Prostate Cancer and a Multiancestry Polygenic Risk Score Associated with Aggressive Disease in Men of African Ancestry. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2023-01-24 | |
dc.date.updated | 2023-06-05T09:51:36Z | |
rioxxterms.version | AM | |
rioxxterms.versionofrecord | 10.1016/j.eururo.2023.01.022 | |
rioxxterms.licenseref.startdate | 2023-02-27 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/36872133 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics | |
pubs.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/18/19 Starting Cohort | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.1016/j.eururo.2023.01.022 | |
icr.researchteam | Oncogenetics | |
dc.contributor.icrauthor | Saunders, Edward | |
dc.contributor.icrauthor | Kote-Jarai, Zsofia | |
dc.contributor.icrauthor | Eeles, Rosalind | |
icr.provenance | Deposited by Miss Fay Allen (impersonating Prof Ros Eeles) on 2023-06-05. Deposit type is initial. No. of files: 1. Files: Manuscript_EURUROL-D-22-00747_R3_clean.docx | |
icr.provenance | Deposited by Mr Arek Surman (impersonating Prof Ros Eeles) on 2023-06-06. Deposit type is subsequent. No. of files: 1. Files: Manuscript_EURUROL-D-22-00747_R3_clean (1).pdf | |