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Prostate cancer pol...
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Klein, Robert J.Department of Genetics and Genomic Sciences and Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, NY, New York, United States,Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Icahn Genom Inst, New York, NY 10029 USA.
(author)
Prostate cancer polygenic risk score and prediction of lethal prostate cancer
- Article/chapterEnglish2022
Publisher, publication year, extent ...
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2022-04-08
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Nature Publishing Group,2022
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:umu-194353
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-194353URI
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https://doi.org/10.1038/s41698-022-00266-8DOI
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https://lup.lub.lu.se/record/e310aaa5-7198-4819-8591-0c25ab1b7868URI
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-473717URI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Vertosick, EmilyDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY, New York, United States,Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 1275 York Ave, New York, NY 10021 USA.(Swepub:lu)em1684ve
(author)
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Sjoberg, DanDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY, New York, United States,Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 1275 York Ave, New York, NY 10021 USA.
(author)
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Ulmert, DavidDepartment 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,Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA USA.;David Geffen UCLA Sch Med, Ahmanson Translat Imaging Div, Los Angeles, CA USA.;David Geffen UCLA Sch Med Los, Jonsson Comprehens Canc Ctr, Los Angeles, CA USA.;Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA USA.;Univ Calif Los Angeles, Inst Urol Oncol, Los Angeles, CA USA.(Swepub:lu)klke-dul
(author)
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Rönn, Ann-CharlotteClinical Research Center, Karolinska University Hospital, Huddinge, Sweden,Karolinska Univ Hosp, Clin Res Ctr, Huddinge, Sweden.
(author)
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Häggström, ChristelUppsala universitet,Uppsala University,Umeå University,Umeå universitet,Enheten för biobanksforskning,Department of Surgical Sciences, Uppsala University, Uppsala, Sweden,Endokrinkirurgi,Umeå Univ, Dept Biobank Res, Umeå, Sweden.(Swepub:uu)chrha650
(author)
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Thysell, ElinUmeå University,Umeå universitet,Patologi,Umeå Univ, Dept Med Biosci, Umeå, Sweden.(Swepub:umu)elnsjn00
(author)
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Hallmans, Göran,1947-Umeå University,Umeå universitet,Avdelningen för hållbar hälsa,Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden.(Swepub:umu)goha0001
(author)
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Dahlin, AndersLund University,Lunds universitet,Internmedicin - epidemiologi,Forskargrupper vid Lunds universitet,Internal Medicine - Epidemiology,Lund University Research Groups,Lund Univ, Dept Clin Sci, Malmö, Sweden.(Swepub:lu)infl-ada
(author)
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Stattin, PärUppsala universitet,Urologkirurgi(Swepub:uu)parst892
(author)
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Melander, OlleLund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups,Skåne University Hospital,Lund Univ, Dept Clin Sci, Malmö, Sweden.;Skane Univ Hosp, Dept Emergency & Internal Med, Malmö, Sweden.(Swepub:lu)endo-ome
(author)
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Vickers, AndrewDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY, New York, United States,Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 1275 York Ave, New York, NY 10021 USA.
(author)
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Lilja, HansLund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Department of Translational Medicine,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Memorial Sloan-Kettering Cancer Center,Mem Sloan Kettering Canc Ctr, Dept Lab Med, 1275 York Ave, New York, NY 10021 USA.;Mem Sloan Kettering Canc Ctr, Dept Surg, 1275 York Ave, New York, NY 10021 USA.;Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA.;Lund Univ, Dept Translat Med, Malmö, Sweden.(Swepub:lu)klke-hli
(author)
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Department of Genetics and Genomic Sciences and Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, NY, New York, United StatesIcahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Icahn Genom Inst, New York, NY 10029 USA.
(creator_code:org_t)
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In:npj Precision Oncology: Nature Publishing Group6:12397-768X
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Klein, Robert J.
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Vertosick, Emily
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Sjoberg, Dan
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Ulmert, David
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Rönn, Ann-Charlo ...
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Häggström, Chris ...
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Thysell, Elin
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Hallmans, Göran, ...
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Dahlin, Anders
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Stattin, Pär
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Melander, Olle
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Vickers, Andrew
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Lilja, Hans
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