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Prostate cancer polygenic risk score and prediction of lethal prostate cancer
Department of Genetics and Genomic Sciences and Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, NY, New York, United States.
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY, New York, United States.
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY, New York, United States.
Department of Molecular and Medical Pharmacology, University of California Los Angeles, CA, Los Angeles, United States; Ahmanson Translational Imaging Division, David Geffen UCLA School of Medicine, CA, Los Angeles, United States; Jonsson Comprehensive Cancer Center, David Geffen UCLA School of Medicine, CA, Los Angeles, United States; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, CA, Los Angeles, United States; Institute of Urologic Oncology, University of California Los Angeles, CA, Los Angeles, United States.
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2022 (English)In: npj Precision Oncology, E-ISSN 2397-768X, Vol. 6, no 1, article id 25Article in journal (Refereed) Published
Abstract [en]

Polygenic risk scores (PRS) for prostate cancer incidence have been proposed to optimize prostate cancer screening. Prediction of lethal prostate cancer is key to any stratified screening program to avoid excessive overdiagnosis. Herein, PRS for incident prostate cancer was evaluated in two population-based cohorts of unscreened middle-aged men linked to cancer and death registries: the Västerbotten Intervention Project (VIP) and the Malmö Diet and Cancer study (MDC). SNP genotypes were measured by genome-wide SNP genotyping by array followed by imputation or genotyping of selected SNPs using mass spectrometry. The ability of PRS to predict lethal prostate cancer was compared to PSA and a commercialized pre-specified model based on four kallikrein markers. The PRS was associated with incident prostate cancer, replicating previously reported relative risks, and was also associated with prostate cancer death. However, unlike PSA, the PRS did not show stronger association with lethal disease: the hazard ratio for prostate cancer incidence vs. prostate cancer metastasis and death was 1.69 vs. 1.65 in VIP and 1.25 vs. 1.25 in MDC. PSA was a much stronger predictor of prostate cancer metastasis or death with an area-under-the-curve of 0.78 versus 0.63 for the PRS. Importantly, addition of PRS to PSA did not contribute additional risk stratification for lethal prostate cancer. We have shown that a PRS that predicts prostate cancer incidence does not have utility above and beyond that of PSA measured at baseline when applied to the clinically relevant endpoint of prostate cancer death. These findings have implications for public health policies for delivery of prostate cancer screening. Focusing polygenic risk scores on clinically significant endpoints such as prostate cancer metastasis or death would likely improve clinical utility.

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Nature Publishing Group, 2022. Vol. 6, no 1, article id 25
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Cancer and Oncology
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URN: urn:nbn:se:umu:diva-194353DOI: 10.1038/s41698-022-00266-8ISI: 000781349700001PubMedID: 35396534Scopus ID: 2-s2.0-85128179283OAI: oai:DiVA.org:umu-194353DiVA, id: diva2:1655659
Funder
Swedish Cancer Society, 2017/559Swedish Research Council, 2016-02974Available from: 2022-05-03 Created: 2022-05-03 Last updated: 2023-05-24Bibliographically approved

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Häggström, ChristelThysell, ElinHallmans, Göran

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CiteExportLink to record
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