Research Papers:

Exome-based genome-wide association study and risk assessment using genetic risk score to prostate cancer in the Korean population

Jong Jin Oh, Soo Ji Lee, Joo-Yeon Hwang, Dokyoon Kim, Sang Eun Lee, Sung Kyu Hong, Jin-Nyoung Ho, Sungroh Yoon, Joohon Sung, Wun-Jae Kim and Seok-Soo Byun _

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Oncotarget. 2017; 8:43934-43943. https://doi.org/10.18632/oncotarget.16540

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Jong Jin Oh1,*, Soo Ji Lee2,*, Joo-Yeon Hwang3,*, Dokyoon Kim4, Sang Eun Lee1, Sung Kyu Hong1, Jin-Nyoung Ho1,5, Sungroh Yoon6, Joohon Sung2, Wun-Jae Kim7 and Seok-Soo Byun1

1Department of Urology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea

2Complex Disease and Genome Epidemiology Branch, Department of Public Health, Graduate School of Public Health, Seoul National University, Seoul, Korea

3Division of Structural & Functional genomics, Center for Genome Science, Korean National Institute of Health, KCDC, Korea

4Department of Biomedical and Translational Informatics, Geisinger Health System, Danville, PA, USA

5Biomedical Research Institute, Seoul National University Bundang Hospital, Seongnam, Korea

6Department of Electrical and Computer Engineering, Seoul National University, Seoul, Korea

7Department of Urology, Chung Buk National University Hospital, Cheongju, Korea

*Authors contributed equally in this work

Correspondence to:

Seok-Soo Byun, email: [email protected]

Wun-Jae Kim, email: [email protected]

Keywords: prostate, prostate cancer, exome, Korean

Received: December 15, 2016    Accepted: February 15, 2017    Published: March 24, 2017


Purpose: To investigate exome-wide genetic variants associated with prostate cancer (PCa) in Koreans and evaluate the discriminative ability by the genetic risk score (GRS).

Patients and methods: We prospectively recruited 1,001 PCa cases from a tertiary hospital and conducted a case-control study including 2,641 healthy men (Stage I). Participants were analyzed using HumanExome BeadChip. For the external validation, additionally enrolled 514 PCa cases and 548 controls (independent cohort) were analyzed for the identified single nucleotide polymorphisms (SNPs) of Stage I (Stage II). The GRS was calculated as a non-weighted sum of the risk allele counts and investigated for accuracy of prediction of PCa.

Results: the mean age was 66.3 years, and the median level of prostate specific antigen (PSA) was 9.19 ng/ml in PCa cases. In Stage I, 4 loci containing 5 variants (rs1512268 on 8p21.2; rs1016343 and rs7837688 on 8q24.21; rs7501939 on 17q12, and rs2735839 on 19q13.33) were confirmed to reach exome-wide significance (p<8.3x10-7). In Stage II, the mean GRS was 4.23 ± 1.44 for the controls and 4.78 ± 1.43 for the cases. As a reference to GRS 4, GRS 6, 7 and 8 showed a statistically significant risk of PCa (OR=1.85, 2.11 and 3.34, respectively).

Conclusions: The five variants were validated to associate with PCa in firstly performed exome-wide study in Koreans. The addition of individualized calculated GRS effectively enhanced the accuracy of prediction. These results need to be validated in future studies.

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