A Polygenic Risk Score Predicts Incident Prostate Cancer Risk in Older Men but Does Not Select for Clinically Significant Disease

Despite the high prevalence of prostate cancer in older men, the predictive value of a polygenic risk score (PRS) remains uncertain in men aged ≥70 years. We used a 6.6 million-variant PRS to predict the risk of incident prostate cancer in a prospective study of 5701 men of European descent aged ≥70...

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Autores principales:	Andrew Bakshi, Moeen Riaz, Suzanne G. Orchard, Prudence R. Carr, Amit D. Joshi, Yin Cao, Richard Rebello, Tú Nguyen-Dumont, Melissa C. Southey, Jeremy L. Millar, Lucy Gately, Peter Gibbs, Leslie G. Ford, Howard L. Parnes, Andrew T. Chan, John J. McNeil, Paul Lacaze
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	prostate cancer polygenic risk score Gleason grade Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/a8ca762ddd664e1c850cc3d6c9ef4b84
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spelling	oai:doaj.org-article:a8ca762ddd664e1c850cc3d6c9ef4b842021-11-25T17:04:21ZA Polygenic Risk Score Predicts Incident Prostate Cancer Risk in Older Men but Does Not Select for Clinically Significant Disease10.3390/cancers132258152072-6694https://doaj.org/article/a8ca762ddd664e1c850cc3d6c9ef4b842021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5815https://doaj.org/toc/2072-6694Despite the high prevalence of prostate cancer in older men, the predictive value of a polygenic risk score (PRS) remains uncertain in men aged ≥70 years. We used a 6.6 million-variant PRS to predict the risk of incident prostate cancer in a prospective study of 5701 men of European descent aged ≥70 years (mean age 75 years) enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) clinical trial. The study endpoint was prostate cancer, including metastatic or non-metastatic disease, confirmed by an expert panel. After excluding participants with a history of prostate cancer at enrolment, we used a multivariable Cox proportional hazards model to assess the association between the PRS and incident prostate cancer risk, adjusting for covariates. Additionally, we examined the distribution of Gleason grade groups by PRS group to determine if a higher PRS was associated with higher grade disease. We tested for interaction between the PRS and aspirin treatment. Logistic regression was used to independently assess the association of the PRS with prevalent (pre-trial) prostate cancer, reported in medical histories. During a median follow-up time of 4.6 years, 218 of the 5701 participants (3.8%) were diagnosed with prostate cancer. The PRS predicted incident risk with a hazard ratio (HR) of 1.52 per standard deviation (SD) (95% confidence interval (CI) 1.33–1.74, <i>p</i> < 0.001). Men in the top quintile of the PRS distribution had an almost three times higher risk of prostate cancer than men in the lowest quintile (HR = 2.99 (95% CI 1.90–4.27), <i>p</i> < 0.001). However, a higher PRS was not associated with a higher Gleason grade groups. We found no interaction between aspirin treatment and the PRS for prostate cancer risk. The PRS was also associated with prevalent prostate cancer (odds ratio = 1.80 per SD (95% CI 1.65–1.96), <i>p</i> < 0.001).While a PRS for prostate cancer is strongly associated with incident risk in men aged ≥70 years, the clinical utility of the PRS as a biomarker is currently limited by its inability to select for clinically significant disease.Andrew BakshiMoeen RiazSuzanne G. OrchardPrudence R. CarrAmit D. JoshiYin CaoRichard RebelloTú Nguyen-DumontMelissa C. SoutheyJeremy L. MillarLucy GatelyPeter GibbsLeslie G. FordHoward L. ParnesAndrew T. ChanJohn J. McNeilPaul LacazeMDPI AGarticleprostate cancerpolygenic risk scoreGleason gradeNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5815, p 5815 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	prostate cancer polygenic risk score Gleason grade Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	prostate cancer polygenic risk score Gleason grade Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Andrew Bakshi Moeen Riaz Suzanne G. Orchard Prudence R. Carr Amit D. Joshi Yin Cao Richard Rebello Tú Nguyen-Dumont Melissa C. Southey Jeremy L. Millar Lucy Gately Peter Gibbs Leslie G. Ford Howard L. Parnes Andrew T. Chan John J. McNeil Paul Lacaze A Polygenic Risk Score Predicts Incident Prostate Cancer Risk in Older Men but Does Not Select for Clinically Significant Disease
description	Despite the high prevalence of prostate cancer in older men, the predictive value of a polygenic risk score (PRS) remains uncertain in men aged ≥70 years. We used a 6.6 million-variant PRS to predict the risk of incident prostate cancer in a prospective study of 5701 men of European descent aged ≥70 years (mean age 75 years) enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) clinical trial. The study endpoint was prostate cancer, including metastatic or non-metastatic disease, confirmed by an expert panel. After excluding participants with a history of prostate cancer at enrolment, we used a multivariable Cox proportional hazards model to assess the association between the PRS and incident prostate cancer risk, adjusting for covariates. Additionally, we examined the distribution of Gleason grade groups by PRS group to determine if a higher PRS was associated with higher grade disease. We tested for interaction between the PRS and aspirin treatment. Logistic regression was used to independently assess the association of the PRS with prevalent (pre-trial) prostate cancer, reported in medical histories. During a median follow-up time of 4.6 years, 218 of the 5701 participants (3.8%) were diagnosed with prostate cancer. The PRS predicted incident risk with a hazard ratio (HR) of 1.52 per standard deviation (SD) (95% confidence interval (CI) 1.33–1.74, <i>p</i> < 0.001). Men in the top quintile of the PRS distribution had an almost three times higher risk of prostate cancer than men in the lowest quintile (HR = 2.99 (95% CI 1.90–4.27), <i>p</i> < 0.001). However, a higher PRS was not associated with a higher Gleason grade groups. We found no interaction between aspirin treatment and the PRS for prostate cancer risk. The PRS was also associated with prevalent prostate cancer (odds ratio = 1.80 per SD (95% CI 1.65–1.96), <i>p</i> < 0.001).While a PRS for prostate cancer is strongly associated with incident risk in men aged ≥70 years, the clinical utility of the PRS as a biomarker is currently limited by its inability to select for clinically significant disease.
format	article
author	Andrew Bakshi Moeen Riaz Suzanne G. Orchard Prudence R. Carr Amit D. Joshi Yin Cao Richard Rebello Tú Nguyen-Dumont Melissa C. Southey Jeremy L. Millar Lucy Gately Peter Gibbs Leslie G. Ford Howard L. Parnes Andrew T. Chan John J. McNeil Paul Lacaze
author_facet	Andrew Bakshi Moeen Riaz Suzanne G. Orchard Prudence R. Carr Amit D. Joshi Yin Cao Richard Rebello Tú Nguyen-Dumont Melissa C. Southey Jeremy L. Millar Lucy Gately Peter Gibbs Leslie G. Ford Howard L. Parnes Andrew T. Chan John J. McNeil Paul Lacaze
author_sort	Andrew Bakshi
title	A Polygenic Risk Score Predicts Incident Prostate Cancer Risk in Older Men but Does Not Select for Clinically Significant Disease
title_short	A Polygenic Risk Score Predicts Incident Prostate Cancer Risk in Older Men but Does Not Select for Clinically Significant Disease
title_full	A Polygenic Risk Score Predicts Incident Prostate Cancer Risk in Older Men but Does Not Select for Clinically Significant Disease
title_fullStr	A Polygenic Risk Score Predicts Incident Prostate Cancer Risk in Older Men but Does Not Select for Clinically Significant Disease
title_full_unstemmed	A Polygenic Risk Score Predicts Incident Prostate Cancer Risk in Older Men but Does Not Select for Clinically Significant Disease
title_sort	polygenic risk score predicts incident prostate cancer risk in older men but does not select for clinically significant disease
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a8ca762ddd664e1c850cc3d6c9ef4b84
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A Polygenic Risk Score Predicts Incident Prostate Cancer Risk in Older Men but Does Not Select for Clinically Significant Disease

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