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Genetic risk assessment of lethal prostate cancer using polygenic risk score and hereditary cancer susceptibility genes

BACKGROUND: The genetic risk of aggressive prostate cancer (PCa) is hard to be assessed due to the lack of aggressiveness-related single-nucleotide polymorphisms (SNPs). Prostate volume (PV) is a potential well-established risk factor for aggressive PCa, we hypothesize that polygenic risk score (PRS...

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Autores principales: Ruan, Xiaohao, Huang, Da, Huang, Jingyi, Tsu, James Hok-Leung, Na, Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10327136/
https://www.ncbi.nlm.nih.gov/pubmed/37415201
http://dx.doi.org/10.1186/s12967-023-04316-y
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author Ruan, Xiaohao
Huang, Da
Huang, Jingyi
Tsu, James Hok-Leung
Na, Rong
author_facet Ruan, Xiaohao
Huang, Da
Huang, Jingyi
Tsu, James Hok-Leung
Na, Rong
author_sort Ruan, Xiaohao
collection PubMed
description BACKGROUND: The genetic risk of aggressive prostate cancer (PCa) is hard to be assessed due to the lack of aggressiveness-related single-nucleotide polymorphisms (SNPs). Prostate volume (PV) is a potential well-established risk factor for aggressive PCa, we hypothesize that polygenic risk score (PRS) based on benign prostate hyperplasia (BPH) or PV-related SNPs may also predict the risk of aggressive PCa or PCa death. METHODS: We evaluated a PRS using 21 BPH/PV-associated SNPs, two established PCa risk-related PRS and 10 guideline-recommended hereditary cancer risk genes in the population-based UK Biobank cohort (N = 209,502). RESULTS: The BPH/PV PRS was significantly inversely associated with the incidence of lethal PCa as well as the natural progress in PCa patients (hazard ratio, HR = 0.92, 95% confidence interval [CI]: 0.87–0.98, P = 0.02; HR = 0.92, 95% CI 0.86–0.98, P = 0.01). Compared with men at the top 25th PRS, PCa patients with bottom 25(th) PRS would have a 1.41-fold (HR, 95% CI 1.16–1.69, P = 0.001) increased PCa fatal risk and shorter survival time at 0.37 yr (95% CI 0.14–0.61, P = 0.002). In addition, patients with BRCA2 or PALB2 pathogenic mutations would also have a high risk of PCa death (HR = 3.90, 95% CI 2.34–6.51, P = 1.79 × 10(–7); HR = 4.29, 95% CI 1.36–13.50, P = 0.01, respectively). However, no interactive but independent effects were detected between this PRS and pathogenic mutations. CONCLUSIONS: Our findings provide a new measurement of PCa patients’ natural disease outcomes via genetic risk ways. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-023-04316-y.
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spelling pubmed-103271362023-07-08 Genetic risk assessment of lethal prostate cancer using polygenic risk score and hereditary cancer susceptibility genes Ruan, Xiaohao Huang, Da Huang, Jingyi Tsu, James Hok-Leung Na, Rong J Transl Med Research BACKGROUND: The genetic risk of aggressive prostate cancer (PCa) is hard to be assessed due to the lack of aggressiveness-related single-nucleotide polymorphisms (SNPs). Prostate volume (PV) is a potential well-established risk factor for aggressive PCa, we hypothesize that polygenic risk score (PRS) based on benign prostate hyperplasia (BPH) or PV-related SNPs may also predict the risk of aggressive PCa or PCa death. METHODS: We evaluated a PRS using 21 BPH/PV-associated SNPs, two established PCa risk-related PRS and 10 guideline-recommended hereditary cancer risk genes in the population-based UK Biobank cohort (N = 209,502). RESULTS: The BPH/PV PRS was significantly inversely associated with the incidence of lethal PCa as well as the natural progress in PCa patients (hazard ratio, HR = 0.92, 95% confidence interval [CI]: 0.87–0.98, P = 0.02; HR = 0.92, 95% CI 0.86–0.98, P = 0.01). Compared with men at the top 25th PRS, PCa patients with bottom 25(th) PRS would have a 1.41-fold (HR, 95% CI 1.16–1.69, P = 0.001) increased PCa fatal risk and shorter survival time at 0.37 yr (95% CI 0.14–0.61, P = 0.002). In addition, patients with BRCA2 or PALB2 pathogenic mutations would also have a high risk of PCa death (HR = 3.90, 95% CI 2.34–6.51, P = 1.79 × 10(–7); HR = 4.29, 95% CI 1.36–13.50, P = 0.01, respectively). However, no interactive but independent effects were detected between this PRS and pathogenic mutations. CONCLUSIONS: Our findings provide a new measurement of PCa patients’ natural disease outcomes via genetic risk ways. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-023-04316-y. BioMed Central 2023-07-06 /pmc/articles/PMC10327136/ /pubmed/37415201 http://dx.doi.org/10.1186/s12967-023-04316-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Ruan, Xiaohao
Huang, Da
Huang, Jingyi
Tsu, James Hok-Leung
Na, Rong
Genetic risk assessment of lethal prostate cancer using polygenic risk score and hereditary cancer susceptibility genes
title Genetic risk assessment of lethal prostate cancer using polygenic risk score and hereditary cancer susceptibility genes
title_full Genetic risk assessment of lethal prostate cancer using polygenic risk score and hereditary cancer susceptibility genes
title_fullStr Genetic risk assessment of lethal prostate cancer using polygenic risk score and hereditary cancer susceptibility genes
title_full_unstemmed Genetic risk assessment of lethal prostate cancer using polygenic risk score and hereditary cancer susceptibility genes
title_short Genetic risk assessment of lethal prostate cancer using polygenic risk score and hereditary cancer susceptibility genes
title_sort genetic risk assessment of lethal prostate cancer using polygenic risk score and hereditary cancer susceptibility genes
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10327136/
https://www.ncbi.nlm.nih.gov/pubmed/37415201
http://dx.doi.org/10.1186/s12967-023-04316-y
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