Genetically adjusted PSA levels for prostate cancer screening
(2023) In Nature Medicine 29(6). p.1412-1423- Abstract
Prostate-specific antigen (PSA) screening for prostate cancer remains controversial because it increases overdiagnosis and overtreatment of clinically insignificant tumors. Accounting for genetic determinants of constitutive, non-cancer-related PSA variation has potential to improve screening utility. In this study, we discovered 128 genome-wide significant associations (P < 5 × 10
-8) in a multi-ancestry meta-analysis of 95,768 men and developed a PSA polygenic score (PGS
PSA) that explains 9.61% of constitutive PSA variation. We found that, in men of European ancestry, using PGS-adjusted PSA would avoid up to 31% of negative prostate biopsies but also result in 12% fewer biopsies in patients with prostate cancer, mostly... (More)Prostate-specific antigen (PSA) screening for prostate cancer remains controversial because it increases overdiagnosis and overtreatment of clinically insignificant tumors. Accounting for genetic determinants of constitutive, non-cancer-related PSA variation has potential to improve screening utility. In this study, we discovered 128 genome-wide significant associations (P < 5 × 10
(Less)
-8) in a multi-ancestry meta-analysis of 95,768 men and developed a PSA polygenic score (PGS
PSA) that explains 9.61% of constitutive PSA variation. We found that, in men of European ancestry, using PGS-adjusted PSA would avoid up to 31% of negative prostate biopsies but also result in 12% fewer biopsies in patients with prostate cancer, mostly with Gleason score <7 tumors. Genetically adjusted PSA was more predictive of aggressive prostate cancer (odds ratio (OR) = 3.44, P = 6.2 × 10
-14, area under the curve (AUC) = 0.755) than unadjusted PSA (OR = 3.31, P = 1.1 × 10
-12, AUC = 0.738) in 106 cases and 23,667 controls. Compared to a prostate cancer PGS alone (AUC = 0.712), including genetically adjusted PSA improved detection of aggressive disease (AUC = 0.786, P = 7.2 × 10
-4). Our findings highlight the potential utility of incorporating PGS for personalized biomarkers in prostate cancer screening.
- author
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Medicine
- volume
- 29
- issue
- 6
- pages
- 1412 - 1423
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:37264206
- scopus:85160847402
- ISSN
- 1546-170X
- DOI
- 10.1038/s41591-023-02277-9
- language
- English
- LU publication?
- yes
- additional info
- © 2023. The Author(s).
- id
- 4bae3c8d-b5ed-49b2-852b-fa4559427b24
- date added to LUP
- 2023-06-10 12:11:14
- date last changed
- 2025-02-11 10:27:34
@article{4bae3c8d-b5ed-49b2-852b-fa4559427b24, abstract = {{<p>Prostate-specific antigen (PSA) screening for prostate cancer remains controversial because it increases overdiagnosis and overtreatment of clinically insignificant tumors. Accounting for genetic determinants of constitutive, non-cancer-related PSA variation has potential to improve screening utility. In this study, we discovered 128 genome-wide significant associations (P < 5 × 10<br> -8) in a multi-ancestry meta-analysis of 95,768 men and developed a PSA polygenic score (PGS<br> PSA) that explains 9.61% of constitutive PSA variation. We found that, in men of European ancestry, using PGS-adjusted PSA would avoid up to 31% of negative prostate biopsies but also result in 12% fewer biopsies in patients with prostate cancer, mostly with Gleason score <7 tumors. Genetically adjusted PSA was more predictive of aggressive prostate cancer (odds ratio (OR) = 3.44, P = 6.2 × 10<br> -14, area under the curve (AUC) = 0.755) than unadjusted PSA (OR = 3.31, P = 1.1 × 10<br> -12, AUC = 0.738) in 106 cases and 23,667 controls. Compared to a prostate cancer PGS alone (AUC = 0.712), including genetically adjusted PSA improved detection of aggressive disease (AUC = 0.786, P = 7.2 × 10<br> -4). Our findings highlight the potential utility of incorporating PGS for personalized biomarkers in prostate cancer screening.<br> </p>}}, author = {{Kachuri, Linda and Hoffmann, Thomas J and Jiang, Yu and Berndt, Sonja I and Shelley, John P and Schaffer, Kerry R and Machiela, Mitchell J and Freedman, Neal D and Huang, Wen-Yi and Li, Shengchao A and Easterlin, Ryder and Goodman, Phyllis J and Till, Cathee and Thompson, Ian and Lilja, Hans and Van Den Eeden, Stephen K and Chanock, Stephen J and Haiman, Christopher A and Conti, David V and Klein, Robert J and Mosley, Jonathan D and Graff, Rebecca E and Witte, John S}}, issn = {{1546-170X}}, language = {{eng}}, number = {{6}}, pages = {{1412--1423}}, publisher = {{Nature Publishing Group}}, series = {{Nature Medicine}}, title = {{Genetically adjusted PSA levels for prostate cancer screening}}, url = {{http://dx.doi.org/10.1038/s41591-023-02277-9}}, doi = {{10.1038/s41591-023-02277-9}}, volume = {{29}}, year = {{2023}}, }