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Sci Rep. 2019 Nov 20;9(1):17173. doi: 10.1038/s41598-019-53445-2.

An exome-wide rare variant analysis of Korean men identifies three novel genes predisposing to prostate cancer.

Author information

1
Department of Urology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
2
Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
3
Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
4
Department of Biomedical Informatics, University of Utah, University of Utah School of Medicine, Salt Lake City, UT, USA.
5
Complex Diseases and Genome Epidemiology Laboratory, Department of Public Health, Graduate School of Public Health, Seoul National University, Seoul, Korea.
6
Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Dokyoon.Kim@pennmedicine.upenn.edu.
7
Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, PA, USA. Dokyoon.Kim@pennmedicine.upenn.edu.
8
Department of Urology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. ssbyun@snubh.org.

Abstract

Since prostate cancer is highly heritable, common variants associated with prostate cancer have been studied in various populations, including those in Korea. However, rare and low-frequency variants have a significant influence on the heritability of the disease. The contributions of rare variants to prostate cancer susceptibility have not yet been systematically evaluated in a Korean population. In this work, we present a large-scale exome-wide rare variant analysis of 7,258 individuals (985 cases with prostate cancer and 6,273 controls). In total, 19 rare variant loci spanning 7 genes contributed to an association with prostate cancer susceptibility. In addition to replicating previously known susceptibility genes (e.g., CDYL2, MST1R, GPER1, and PARD3B), 3 novel genes were identified (FDR q < 0.05), including the non-coding RNAs ENTPD3-AS1, LOC102724438, and protein-coding gene SPATA3. Additionally, 6 pathways were identified based on identified variants and genes, including estrogen signaling pathway, signaling by MST1, IL-15 production, MSP-RON signaling pathway, and IL-12 signaling and production in macrophages, which are known to be associated with prostate cancer. In summary, we report novel genes and rare variants that potentially play a role in prostate cancer susceptibility in the Korean population. These observations demonstrated a path towards one of the fundamental goals of precision medicine, which is to identify biomarkers for a subset of the population with a greater risk of disease than others.

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