Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Addition of a Genetic Risk Score for Identification of Men with a Low Prostate-specific Antigen Level in Midlife at Risk of Developing Lethal Prostate Cancer

Ma, Chaoran ; Ericsson, Caroline ; Carlsson, Sigrid V. LU ; Lilja, Hans LU orcid ; Kibel, Adam ; Graff, Rebecca E. ; Plym, Anna ; Giovannucci, Edward ; Mucci, Lorelei A. and Preston, Mark A. , et al. (2023) In European Urology Open Science 50. p.27-30
Abstract

Men with a low prostate-specific antigen (PSA) level (<1 ng/ml) in midlife may extend the rescreening interval (if aged 40–59 yr) or forgo future PSA screening (if aged >60 yr) owing to their low risk of aggressive prostate cancer (PCa). However, there is a subset of men who develop lethal PCa despite low baseline PSA. We investigated how a PCa polygenic risk score (PRS) in addition to baseline PSA impacts the prediction of lethal PCa among 483 men aged 40–70 yr from the Physicians’ Health Study followed over a median of 33 yr. We examined the association of the PRS with the risk of lethal PCa (lethal cases vs controls) using logistic regression adjusted for baseline PSA. The PCa PRS was associated with risk of lethal PCa (odds... (More)

Men with a low prostate-specific antigen (PSA) level (<1 ng/ml) in midlife may extend the rescreening interval (if aged 40–59 yr) or forgo future PSA screening (if aged >60 yr) owing to their low risk of aggressive prostate cancer (PCa). However, there is a subset of men who develop lethal PCa despite low baseline PSA. We investigated how a PCa polygenic risk score (PRS) in addition to baseline PSA impacts the prediction of lethal PCa among 483 men aged 40–70 yr from the Physicians’ Health Study followed over a median of 33 yr. We examined the association of the PRS with the risk of lethal PCa (lethal cases vs controls) using logistic regression adjusted for baseline PSA. The PCa PRS was associated with risk of lethal PCa (odds ratio per 1 standard deviation in PRS [OR] 1.79, 95% confidence interval [CI] 1.28–2.49). The association between the PRS and lethal PCa was stronger for those with PSA <1 ng/ml (OR 2.23, 95% CI 1.19–4.21) than for men with PSA ≥1 ng/ml (OR 1.61, 95% CI 1.07–2.42). Our PCa PRS improved the identification of men with PSA <1 ng/ml at greater risk of future lethal PCa who should consider ongoing PSA testing. Patient summary: A subset of men develop fatal prostate cancer despite having low prostate-specific antigen (PSA) levels in middle age. A risk score based on multiple genes can help in predicting men who may be at risk of developing lethal prostate cancer and who should be advised to have regular PSA measurements.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Lethal prostate cancer, Polygenic risk score, Prostate-specific antigen
in
European Urology Open Science
volume
50
pages
27 - 30
publisher
Elsevier
external identifiers
  • pmid:36861107
  • scopus:85148727943
ISSN
2666-1691
DOI
10.1016/j.euros.2023.01.012
language
English
LU publication?
yes
additional info
Funding Information: Funding/Support and role of the sponsor: This study was funded by the Department of Defense (W81XWH-19-1-0708, M.A.P.) and the National Institutes of Health/National Cancer Institute (P30-CA008748, S.V.C and H.L.; K22-CA234400, S.V.C.). Physicians’ Health Study PSA data generation was supported by the Department of Defense (W81XWH-18-1-0158). The sponsor played a role in manuscript preparation. K.L.P., M.A.P., and R.E.G. are Prostate Cancer Foundation young investigators. The content is solely the responsibility of the authors and does not necessarily represent the official views of the sponsors. Publisher Copyright: © 2023 The Authors
id
e50ffb64-ebd0-4031-b7d4-2d3f511f3539
date added to LUP
2023-03-16 18:11:29
date last changed
2024-06-13 10:27:48
@article{e50ffb64-ebd0-4031-b7d4-2d3f511f3539,
  abstract     = {{<p>Men with a low prostate-specific antigen (PSA) level (&lt;1 ng/ml) in midlife may extend the rescreening interval (if aged 40–59 yr) or forgo future PSA screening (if aged &gt;60 yr) owing to their low risk of aggressive prostate cancer (PCa). However, there is a subset of men who develop lethal PCa despite low baseline PSA. We investigated how a PCa polygenic risk score (PRS) in addition to baseline PSA impacts the prediction of lethal PCa among 483 men aged 40–70 yr from the Physicians’ Health Study followed over a median of 33 yr. We examined the association of the PRS with the risk of lethal PCa (lethal cases vs controls) using logistic regression adjusted for baseline PSA. The PCa PRS was associated with risk of lethal PCa (odds ratio per 1 standard deviation in PRS [OR] 1.79, 95% confidence interval [CI] 1.28–2.49). The association between the PRS and lethal PCa was stronger for those with PSA &lt;1 ng/ml (OR 2.23, 95% CI 1.19–4.21) than for men with PSA ≥1 ng/ml (OR 1.61, 95% CI 1.07–2.42). Our PCa PRS improved the identification of men with PSA &lt;1 ng/ml at greater risk of future lethal PCa who should consider ongoing PSA testing. Patient summary: A subset of men develop fatal prostate cancer despite having low prostate-specific antigen (PSA) levels in middle age. A risk score based on multiple genes can help in predicting men who may be at risk of developing lethal prostate cancer and who should be advised to have regular PSA measurements.</p>}},
  author       = {{Ma, Chaoran and Ericsson, Caroline and Carlsson, Sigrid V. and Lilja, Hans and Kibel, Adam and Graff, Rebecca E. and Plym, Anna and Giovannucci, Edward and Mucci, Lorelei A. and Preston, Mark A. and Penney, Kathryn L.}},
  issn         = {{2666-1691}},
  keywords     = {{Lethal prostate cancer; Polygenic risk score; Prostate-specific antigen}},
  language     = {{eng}},
  pages        = {{27--30}},
  publisher    = {{Elsevier}},
  series       = {{European Urology Open Science}},
  title        = {{Addition of a Genetic Risk Score for Identification of Men with a Low Prostate-specific Antigen Level in Midlife at Risk of Developing Lethal Prostate Cancer}},
  url          = {{http://dx.doi.org/10.1016/j.euros.2023.01.012}},
  doi          = {{10.1016/j.euros.2023.01.012}},
  volume       = {{50}},
  year         = {{2023}},
}