Identification of novel susceptibility loci and genes for prostate cancer risk

• Verfasst von: Wu, Lang [VerfasserIn]
• Verfasst von: Brenner, Hermann [VerfasserIn]
• Titel: Identification of novel susceptibility loci and genes for prostate cancer risk
• Titelzusatz: A transcriptome-wide association study in over 140,000 European descendants
• Verf.angabe: Lang Wu, Jifeng Wang, Qiuyin Cai, Taylor B. Cavazos, Nima C. Emami, Jirong Long, Xiao-Ou Shu, Yingchang Lu, Xingyi Guo, Joshua A. Bauer, Bogdan Pasaniuc, Kathryn L. Penney, Matthew L. Freedman, Bpc3 Cruk, Zsofia Kote-Jarai, John S. Witte, Christopher A. Haiman, Rosalind A. Eeles, and Wei Zheng... Hermann Brenner [und weitere Autoren]
• E-Jahr: 2019
• Jahr: May 17, 2019
• Umfang: 12 S.
• Teil: volume:79
• Teil: year:2019
• Teil: number:13
• Teil: pages:3192-3204
• Teil: extent:12
• Fussnoten: Gesehen am 03.09.2019
• Titel Quelle: Enthalten in: Cancer research
• Ort Quelle: Philadelphia, Pa. : AACR, 1916
• Jahr Quelle: 2019
• Band/Heft Quelle: 79(2019), 13, Seite 3192-3204
• ISSN Quelle: 1538-7445
• DOI: doi:10.1158/0008-5472.CAN-18-3536
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1675769710

Abstract

Genome-wide association studies have identified genetic variants associated with prostate cancer risk. However, these variants explain only a small fraction of the heritable component of prostate cancer risk, and the genes responsible for many of the identified associations remain unknown. To discover novel prostate cancer genetic loci and possible causal genes at previously identified risk loci, we performed a transcriptome-wide association study in 79,194 cases and 61,112 controls of European ancestry. Using data from the Genotype-Tissue Expression Project, we established genetic models to predict gene expression across the transcriptome for both prostate models and cross-tissue models and evaluated model performance using two independent datasets. We identified significant associations for 137 genes at P < 2.61×10-6, a Bonferroni-corrected threshold, including nine genes that remained significant at P < 2.61×10-6 after adjusting for all known prostate cancer risk variants in nearby regions. Of the 128 remaining associated genes, 94 have not yet been reported as potential target genes at known loci. We silenced 14 genes and many showed a consistent effect on viability and colony-forming efficiency in three cell lines. Our study provides substantial new information to advance our understanding of prostate cancer genetics and biology.