| Title: |
Evidence of Novel Susceptibility Variants for Prostate Cancer and a Multiancestry Polygenic Risk Score Associated with Aggressive Disease in Men of African Ancestry. |
| Authors: |
Chen, F; Madduri, RK; Rodriguez, AA; Darst, BF; Chou, A; Sheng, X; Wang, A; Shen, J; Saunders, EJ; Rhie, SK; Bensen, JT; Ingles, SA; Kittles, RA; Strom, SS; Rybicki, BA; Nemesure, B; Isaacs, WB; Stanford, JL; Zheng, W; Sanderson, M; John, EM; Park, JY; Xu, J; Wang, Y; Berndt, SI; Huff, CD; Yeboah, ED; Tettey, Y; Lachance, J; Tang, W; Rentsch, CT; Cho, K; Mcmahon, BH; Biritwum, RB; Adjei, AA; Tay, E; Truelove, A; Niwa, S; Sellers, TA; Yamoah, K; Murphy, AB; Crawford, DC; Patel, AV; Bush, WS; Aldrich, MC; Cussenot, O; Petrovics, G; Cullen, J; Neslund-Dudas, CM; Stern, MC; Kote-Jarai, Z; Govindasami, K; Cook, MB; Chokkalingam, AP; Hsing, AW; Goodman, PJ; Hoffmann, TJ; Drake, BF; Hu, JJ; Keaton, JM; Hellwege, JN; Clark, PE; Jalloh, M; Gueye, SM; Niang, L; Ogunbiyi, O; Idowu, MO; Popoola, O; Adebiyi, AO; Aisuodionoe-Shadrach, OI; Ajibola, HO; Jamda, MA; Oluwole, OP; Nwegbu, M; Adusei, B; Mante, S; Darkwa-Abrahams, A; Mensah, JE; Diop, H; Van Den Eeden, SK; Blanchet, P; Fowke, JH; Casey, G; Hennis, AJ; Lubwama, A; Thompson, IM; Leach, R; Easton, DF; Preuss, MH; Loos, RJ; Gundell, SM; Wan, P; Mohler, JL; Fontham, ET; Smith, GJ; Taylor, JA; Srivastava, S; Eeles, RA; Carpten, JD; Kibel, AS; Multigner, L; Parent, M-É; Menegaux, F; Cancel-Tassin, G; Klein, EA; Andrews, C; Rebbeck, TR; Brureau, L; Ambs, S; Edwards, TL; Watya, S; Chanock, SJ; Witte, JS; Blot, WJ; Michael Gaziano, J; Justice, AC; Conti, DV; Haiman, CA |
| Contributors: |
Saunders, Edward; Kote-Jarai, Zsofia; Eeles, Rosalind |
| Publisher Information: |
ELSEVIER |
| Publication Year: |
2023 |
| Collection: |
The Institute of Cancer Research (ICR): Publications Repository |
| Subject Terms: |
African ancestry; Aggressive prostate cancer; Polygenic risk score; Prostate cancer; Susceptibility loci |
| Subject Geographic: |
Switzerland |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
Print-Electronic; S0302-2838(23)02561-7 -; application/pdf |
| Language: |
English |
| ISSN: |
1873-7560; 0302-2838 |
| Relation: |
S0302-2838(23)02561-7; European Urology, 2023, pp. S0302-2838(23)02561-7 -; https://repository.icr.ac.uk/handle/internal/5826 |
| DOI: |
10.1016/j.eururo.2023.01.022 |
| Availability: |
https://doi.org/10.1016/j.eururo.2023.01.022; https://repository.icr.ac.uk/handle/internal/5826 |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.AA8041BF |
| Database: |
BASE |