Ahmed, M; Goh, C; Saunders, E; Cieza-Borrella, C; Kote-Jarai, Z; Schumacher, FR; Eeles, R
(2020)
Germline genetic variation in prostate susceptibility does not predict outcomes in the chemoprevention trials PCPT and SELECT.
Prostate Cancer and Prostatic Diseases, 23 (2).
pp. 333-342.
ISSN 1365-7852
https://doi.org/10.1038/s41391-019-0181-y
SGUL Authors: Cieza-Borrella, Clara Isabel
Abstract
Background
The development of prostate cancer can be influenced by genetic and environmental factors. Numerous germline SNPs influence prostate cancer susceptibility. The functional pathways in which these SNPs increase prostate cancer susceptibility are unknown. Finasteride is currently not being used routinely as a chemoprevention agent but the long term outcomes of the PCPT trial are awaited. The outcomes of the SELECT trial have not recommended the use of chemoprevention in preventing prostate cancer. This study investigated whether germline risk SNPs could be used to predict outcomes in the PCPT and SELECT trial.
Methods
Genotyping was performed in European men entered into the PCPT trial (n = 2434) and SELECT (n = 4885). Next generation genotyping was performed using Affymetrix® Eureka™ Genotyping protocols. Logistic regression models were used to test the association of risk scores and the outcomes in the PCPT and SELECT trials.
Results
Of the 100 SNPs, 98 designed successfully and genotyping was validated for samples genotyped on other platforms. A number of SNPs predicted for aggressive disease in both trials. Men with a higher polygenic score are more likely to develop prostate cancer in both trials, but the score did not predict for other outcomes in the trial.
Conclusion
Men with a higher polygenic risk score are more likely to develop prostate cancer. There were no interactions of these germline risk SNPs and the chemoprevention agents in the SELECT and PCPT trials.
Item Type: |
Article
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Additional Information: |
© The Author(s), under exclusive licence to Springer Nature Limited 2019. This article is published with open access.
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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
Keywords: |
1112 Oncology and Carcinogenesis, Urology & Nephrology |
SGUL Research Institute / Research Centre: |
Academic Structure > Institute of Medical & Biomedical Education (IMBE) Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Biomedical Education (INMEBE) |
Journal or Publication Title: |
Prostate Cancer and Prostatic Diseases |
ISSN: |
1365-7852 |
Language: |
en |
Dates: |
Date | Event |
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June 2020 | Published | 27 November 2019 | Published Online | 24 June 2019 | Accepted |
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Publisher License: |
Creative Commons: Attribution 4.0 |
Projects: |
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URI: |
https://openaccess.sgul.ac.uk/id/eprint/111854 |
Publisher's version: |
https://doi.org/10.1038/s41391-019-0181-y |
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