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Evaluation of Polygenic Risk Scores for Prediction of Prostate Cancer in Korean Men
AIMS: The purpose of this study is to evaluate an aggregate influence of prostate cancer (PCa) susceptibility variants on the development of PCa in Korean men by using the polygenic risk score (PRS) approach. METHODS: An analysis of 1,001 cases of PCa and 2,641 controls was performed to: (i) identif...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643004/ https://www.ncbi.nlm.nih.gov/pubmed/33194723 http://dx.doi.org/10.3389/fonc.2020.583625 |
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author | Oh, Jong Jin Kim, Eunae Woo, Eunjin Song, Sang Hun Kim, Jung Kwon Lee, Hakmin Lee, Sangchul Hong, Sung Kyu Byun, Seok-Soo |
author_facet | Oh, Jong Jin Kim, Eunae Woo, Eunjin Song, Sang Hun Kim, Jung Kwon Lee, Hakmin Lee, Sangchul Hong, Sung Kyu Byun, Seok-Soo |
author_sort | Oh, Jong Jin |
collection | PubMed |
description | AIMS: The purpose of this study is to evaluate an aggregate influence of prostate cancer (PCa) susceptibility variants on the development of PCa in Korean men by using the polygenic risk score (PRS) approach. METHODS: An analysis of 1,001 cases of PCa and 2,641 controls was performed to: (i) identify potential PCa-related risk loci in Koreans and (ii) validate the cumulative association between these loci and PCa using the PRS. Subgroup analyses based on risk stratification were conducted to better characterize the potential correlation to key PCa-related clinical outcomes (e.g., Gleason score, prostate-specific antigen levels). The results were replicated using 514 cases of PCa and 548 controls from an independent cohort. RESULTS: Genome-wide association analysis from our discovery cohort revealed 11 candidate single-nucleotide polymorphisms (SNPs) associated with PCa showing statistical significance of p < 5.0 × 10(–5). Seven variants were located at 8q24.21 (rs1016343, rs16901979, and rs13252298 in PRNCR1; rs4242384, rs7837688, and rs1447295 in CASC8; and rs1512268 in NKX3). Two variants located within HNF1B (rs7501939 and rs4430796) had a significant negative association with PCa risk [odds ratio (OR) = 0.717 and 0.747, p = 6.42 × 10(–7) and 3.67 × 10(–6), respectively]. Of the six independent SNPs that remained after linkage disequilibrium (LD) pruning, the top four SNPs best predicted PCa risk with an area under the receiver operating characteristic curve (AUC) of 0.637 (95% CI: 0.582–0.692). Those with top 25% polygenic risk had a 4.2-fold increased risk of developing PCa compared with those with low risk. CONCLUSION: Eleven PCa risk variants in Korean men were identified; PRSs of a subset of these variants could help predict PCa susceptibility. |
format | Online Article Text |
id | pubmed-7643004 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-76430042020-11-13 Evaluation of Polygenic Risk Scores for Prediction of Prostate Cancer in Korean Men Oh, Jong Jin Kim, Eunae Woo, Eunjin Song, Sang Hun Kim, Jung Kwon Lee, Hakmin Lee, Sangchul Hong, Sung Kyu Byun, Seok-Soo Front Oncol Oncology AIMS: The purpose of this study is to evaluate an aggregate influence of prostate cancer (PCa) susceptibility variants on the development of PCa in Korean men by using the polygenic risk score (PRS) approach. METHODS: An analysis of 1,001 cases of PCa and 2,641 controls was performed to: (i) identify potential PCa-related risk loci in Koreans and (ii) validate the cumulative association between these loci and PCa using the PRS. Subgroup analyses based on risk stratification were conducted to better characterize the potential correlation to key PCa-related clinical outcomes (e.g., Gleason score, prostate-specific antigen levels). The results were replicated using 514 cases of PCa and 548 controls from an independent cohort. RESULTS: Genome-wide association analysis from our discovery cohort revealed 11 candidate single-nucleotide polymorphisms (SNPs) associated with PCa showing statistical significance of p < 5.0 × 10(–5). Seven variants were located at 8q24.21 (rs1016343, rs16901979, and rs13252298 in PRNCR1; rs4242384, rs7837688, and rs1447295 in CASC8; and rs1512268 in NKX3). Two variants located within HNF1B (rs7501939 and rs4430796) had a significant negative association with PCa risk [odds ratio (OR) = 0.717 and 0.747, p = 6.42 × 10(–7) and 3.67 × 10(–6), respectively]. Of the six independent SNPs that remained after linkage disequilibrium (LD) pruning, the top four SNPs best predicted PCa risk with an area under the receiver operating characteristic curve (AUC) of 0.637 (95% CI: 0.582–0.692). Those with top 25% polygenic risk had a 4.2-fold increased risk of developing PCa compared with those with low risk. CONCLUSION: Eleven PCa risk variants in Korean men were identified; PRSs of a subset of these variants could help predict PCa susceptibility. Frontiers Media S.A. 2020-10-22 /pmc/articles/PMC7643004/ /pubmed/33194723 http://dx.doi.org/10.3389/fonc.2020.583625 Text en Copyright © 2020 Oh, Kim, Woo, Song, Kim, Lee, Lee, Hong and Byun. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Oh, Jong Jin Kim, Eunae Woo, Eunjin Song, Sang Hun Kim, Jung Kwon Lee, Hakmin Lee, Sangchul Hong, Sung Kyu Byun, Seok-Soo Evaluation of Polygenic Risk Scores for Prediction of Prostate Cancer in Korean Men |
title | Evaluation of Polygenic Risk Scores for Prediction of Prostate Cancer in Korean Men |
title_full | Evaluation of Polygenic Risk Scores for Prediction of Prostate Cancer in Korean Men |
title_fullStr | Evaluation of Polygenic Risk Scores for Prediction of Prostate Cancer in Korean Men |
title_full_unstemmed | Evaluation of Polygenic Risk Scores for Prediction of Prostate Cancer in Korean Men |
title_short | Evaluation of Polygenic Risk Scores for Prediction of Prostate Cancer in Korean Men |
title_sort | evaluation of polygenic risk scores for prediction of prostate cancer in korean men |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643004/ https://www.ncbi.nlm.nih.gov/pubmed/33194723 http://dx.doi.org/10.3389/fonc.2020.583625 |
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