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, Seok Soo Byun

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)43934-43943
Number of pages10
JournalOncotarget
Volume8
Issue number27
DOIs
StatePublished - 1 Jan 2017

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Exome
Genome-Wide Association Study
Prostatic Neoplasms
Population
Prostate-Specific Antigen
Tertiary Care Centers
Single Nucleotide Polymorphism
Case-Control Studies
Alleles

Keywords

  • Exome
  • Korean
  • Prostate
  • Prostate cancer

Cite this

Oh, Jong Jin ; Lee, Soo Ji ; Hwang, Joo Yeon ; Kim, Dokyoon ; Lee, Sang Eun ; Hong, Sung Kyu ; Ho, Jin Nyoung ; Yoon, Sungroh ; Sung, Joohon ; Kim, Wun Jae ; Byun, Seok Soo. / Exome-based genome-wide association study and risk assessment using genetic risk score to prostate cancer in the Korean population. In: Oncotarget. 2017 ; Vol. 8, No. 27. pp. 43934-43943.
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title = "Exome-based genome-wide association study and risk assessment using genetic risk score to prostate cancer in the Korean population",
abstract = "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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Exome-based genome-wide association study and risk assessment using genetic risk score to prostate cancer in the Korean population. / Oh, Jong Jin; Lee, Soo Ji; Hwang, Joo Yeon; Kim, Dokyoon; Lee, Sang Eun; Hong, Sung Kyu; Ho, Jin Nyoung; Yoon, Sungroh; Sung, Joohon; Kim, Wun Jae; Byun, Seok Soo.

In: Oncotarget, Vol. 8, No. 27, 01.01.2017, p. 43934-43943.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Exome-based genome-wide association study and risk assessment using genetic risk score to prostate cancer in the Korean population

AU - Oh, Jong Jin

AU - Lee, Soo Ji

AU - Hwang, Joo Yeon

AU - Kim, Dokyoon

AU - Lee, Sang Eun

AU - Hong, Sung Kyu

AU - Ho, Jin Nyoung

AU - Yoon, Sungroh

AU - Sung, Joohon

AU - Kim, Wun Jae

AU - Byun, Seok Soo

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

KW - Exome

KW - Korean

KW - Prostate

KW - Prostate cancer

UR - http://www.scopus.com/inward/record.url?scp=85021826008&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.16540

DO - 10.18632/oncotarget.16540

M3 - Article

AN - SCOPUS:85021826008

VL - 8

SP - 43934

EP - 43943

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

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ER -