Dépôt numérique
RECHERCHER

Evidence of Novel Susceptibility Variants for Prostate Cancer and a Multiancestry Polygenic Risk Score Associated with Aggressive Disease in Men of African Ancestry

Téléchargements

Téléchargements par mois depuis la dernière année

Plus de statistiques...

Chen, Fei; Madduri, Ravi K; Rodriguez, Alex A; Darst, Burcu F; Chou, Alisha; Sheng, Xin; Wang, Anqi; Shen, Jiayi; Saunders, Edward J; Rhie, Suhn K; Bensen, Jeannette T; Ingles, Sue A; Kittles, Rick A; Strom, Sara S.; Rybicki, Benjamin A; Nemesure, Barbara; Isaacs, William B.; Stanford, Janet L; Zheng, Wei; Sanderson, Maureen; John, Esther M; Park, Jong Y; Xu, Jianfeng; Wang, Ying; Berndt, Sonja I; Huff, Chad D; Yeboah, Edward D; Tettey, Yao; Lachance, Joseph; Tang, Wei; Rentsch, Christopher T; Cho, Kelly; McMahon, Benjamin H; Biritwum, Richard B; Adjei, Andrew A.; Tay, Evelyn; Truelove, Ann; Niwa, Shelley; Sellers, Thomas A; Yamoah, Kosj; Murphy, Adam B; Crawford, Dana C; Patel, Alpa V; Bush, William S; Aldrich, Melinda C; Cussenot, Olivier; Petrovics, Gyorgy; Cullen, Jennifer; Neslund-Dudas, Christine M; Stern, Mariana C; Kote-Jarai, Zsofia; Govindasami, Koveela; Cook, Michael B; Chokkalingam, Anand P; Hsing, Ann W.; Goodman, Phyllis J; Hoffmann, Thomas J; Drake, Bettina F; Hu, Jennifer J; Keaton, Jacob M; Hellwege, Jacklyn N; Clark, Peter E; Jalloh, Mohamed; Gueye, Serigne M; Niang, Lamine; Ogunbiyi, Olufemi; Idowu, Michael O; Popoola, Olufemi; Adebiyi, Akindele O; Aisuodionoe-Shadrach, Oseremen I; Ajibola, Hafees O; Jamda, Mustapha A; Oluwole, Olabode P; Nwegbu, Maxwell; Adusei, Ben; Mante, Sunny; Darkwa-Abrahams, Afua; Mensah, James E; Diop, Halimatou; Van Den Eeden, Stephen K; Blanchet, Pascal; Fowke, Jay H; Casey, Graham; Hennis, Anselm J; Lubwama, Alexander; Thompson, Ian M Jr; Leach, Robin; Easton, Douglas F; Preuss, Michael H; Loos, Ruth J; Gundell, Susan M; Wan, Peggy; Mohler, James L; Fontham, Elizabeth T; Smith, Gary J; Taylor, Jack A; Srivastava, Shiv; Eeles, Rosaline A; Carpten, John D; Kibel, Adam S; Multigner, Luc; Parent, Marie-Élise ORCID logoORCID: https://orcid.org/0000-0002-4196-3773; Menegaux, Florence; Cancel-Tassin, Geraldine; Klein, Eric A; Andrews, Caroline; Rebbeck, Timothy R; Brureau, Laurent; Ambs, Stefan; Edwards, Todd L; Watya, Stephen; Chanock, Stephen J; Witte, John S; Blot, William J; Gaziano, Michael J; Justice, Amy C; Conti, David V et Haiman, Christopher A (2023). Evidence of Novel Susceptibility Variants for Prostate Cancer and a Multiancestry Polygenic Risk Score Associated with Aggressive Disease in Men of African Ancestry European Urology , vol. 84 , nº 1. pp. 13-21. DOI: 10.1016/j.eururo.2023.01.022.

[thumbnail of Evidence of Novel Susceptibility Variants for Prostate Cancer and a Multiancestry Polygenic Risk.pdf] PDF - Version publiée
Document sous embargo jusqu'à 20 juillet 2024.

Télécharger (912kB)

Résumé


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.

Type de document: Article
Mots-clés libres: African ancestry; Aggressive prostate cancer; Polygenic risk score; Prostate cancer; Susceptibility loci.
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 08 déc. 2023 21:55
Dernière modification: 08 déc. 2023 21:55
URI: https://espace.inrs.ca/id/eprint/13358

Gestion Actions (Identification requise)

Modifier la notice Modifier la notice