Prostate Cancer (PCa) Risk Variants and Risk of Fatal PCa in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium
Identifieur interne : 001F52 ( Pmc/Corpus ); précédent : 001F51; suivant : 001F53Prostate Cancer (PCa) Risk Variants and Risk of Fatal PCa in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium
Auteurs : Irene M. Shui ; Sara Lindström ; Adam S. Kibel ; Sonja I. Berndt ; Daniele Campa ; Travis Gerke ; Kathryn L. Penney ; Demetrius Albanes ; Christine Berg ; H. Bas Bueno-De-Mesquita ; Stephen Chanock ; E. David Crawford ; W. Ryan Diver ; Susan M. Gapstur ; J. Michael Gaziano ; Graham G. Giles ; Brian Henderson ; Robert Hoover ; Mattias Johansson ; Loic Le Marchand ; Jing Ma ; Carmen Navarro ; Kim Overvad ; Fredrick R. Schumacher ; Gianluca Severi ; Afshan Siddiq ; Meir Stampfer ; Victoria L. Stevens ; Ruth C. Travis ; Dimitrios Trichopoulos ; Paolo Vineis ; Lorelei A. Mucci ; Meredith Yeager ; Edward Giovannucci ; Peter KraftSource :
- European urology [ 0302-2838 ] ; 2014.
Abstract
Screening and diagnosis of prostate cancer (PCa) is hampered by an inability to predict who has the potential to develop fatal disease and who has indolent cancer. Studies have identified multiple genetic risk loci for PCa incidence, but it is unknown whether they could be used as biomarkers for PCa-specific mortality (PCSM).
To examine the association of 47 established PCa risk single-nucleotide polymorphisms (SNPs) with PCSM.
We included 10 487 men who had PCa and 11 024 controls, with a median follow-up of 8.3 yr, during which 1053 PCa deaths occurred.
The main outcome was PCSM. The
Among the cases, we found that 8 of the 47 SNPs were significantly associated (
Eight established risk loci were associated with progression to PCSM after diagnosis. Twenty-two SNPs were associated with fatal PCa incidence, but most did not differentiate between fatal and nonfatal PCa. The relatively small magnitudes of the associations do not translate well into risk prediction, but these findings merit further follow-up, because they may yield important clues about the complex biology of fatal PCa. Patient summary: In this report, we assessed whether established PCa risk variants could predict PCSM. We found eight risk variants associated with PCSM: One predicted an increased risk of PCSM, while seven were associated with decreased risk. Larger studies that focus on fatal PCa are needed to identify more markers that could aid prediction.
Url:
DOI: 10.1016/j.eururo.2013.12.058
PubMed: 24411283
PubMed Central: 4006298
Links to Exploration step
PMC:4006298Le document en format XML
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<author><name sortKey="Shui, Irene M" sort="Shui, Irene M" uniqKey="Shui I" first="Irene M." last="Shui">Irene M. Shui</name>
<affiliation><nlm:aff id="A1">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff>
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<author><name sortKey="Lindstrom, Sara" sort="Lindstrom, Sara" uniqKey="Lindstrom S" first="Sara" last="Lindström">Sara Lindström</name>
<affiliation><nlm:aff id="A1">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff>
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<author><name sortKey="Kibel, Adam S" sort="Kibel, Adam S" uniqKey="Kibel A" first="Adam S." last="Kibel">Adam S. Kibel</name>
<affiliation><nlm:aff id="A2">Department of Surgery, Division of Urology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA</nlm:aff>
</affiliation>
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<author><name sortKey="Berndt, Sonja I" sort="Berndt, Sonja I" uniqKey="Berndt S" first="Sonja I." last="Berndt">Sonja I. Berndt</name>
<affiliation><nlm:aff id="A3">Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Campa, Daniele" sort="Campa, Daniele" uniqKey="Campa D" first="Daniele" last="Campa">Daniele Campa</name>
<affiliation><nlm:aff id="A4">Genomic Epidemiology Group, German Cancer Research Center (Deutsches Krebsforschungszentrum), Heidelberg, Germany</nlm:aff>
</affiliation>
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<author><name sortKey="Gerke, Travis" sort="Gerke, Travis" uniqKey="Gerke T" first="Travis" last="Gerke">Travis Gerke</name>
<affiliation><nlm:aff id="A1">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff>
</affiliation>
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<author><name sortKey="Penney, Kathryn L" sort="Penney, Kathryn L" uniqKey="Penney K" first="Kathryn L." last="Penney">Kathryn L. Penney</name>
<affiliation><nlm:aff id="A1">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A5">Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Albanes, Demetrius" sort="Albanes, Demetrius" uniqKey="Albanes D" first="Demetrius" last="Albanes">Demetrius Albanes</name>
<affiliation><nlm:aff id="A3">Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA</nlm:aff>
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<author><name sortKey="Berg, Christine" sort="Berg, Christine" uniqKey="Berg C" first="Christine" last="Berg">Christine Berg</name>
<affiliation><nlm:aff id="A6">Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medicine, Baltimore, MD, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bueno De Mesquita, H Bas" sort="Bueno De Mesquita, H Bas" uniqKey="Bueno De Mesquita H" first="H. Bas" last="Bueno-De-Mesquita">H. Bas Bueno-De-Mesquita</name>
<affiliation><nlm:aff id="A7">National Institute for Public Health and the Environment, Bilthoven, The Netherlands</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A8">Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A28">School of Public Health, Imperial College London, London, United Kingdom</nlm:aff>
</affiliation>
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<author><name sortKey="Chanock, Stephen" sort="Chanock, Stephen" uniqKey="Chanock S" first="Stephen" last="Chanock">Stephen Chanock</name>
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<affiliation><nlm:aff id="A9">Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Gaithersburg, MD, USA</nlm:aff>
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<author><name sortKey="Crawford, E David" sort="Crawford, E David" uniqKey="Crawford E" first="E. David" last="Crawford">E. David Crawford</name>
<affiliation><nlm:aff id="A10">Urologic Oncology, University of Colorado, Denver, CO, USA</nlm:aff>
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<author><name sortKey="Diver, W Ryan" sort="Diver, W Ryan" uniqKey="Diver W" first="W. Ryan" last="Diver">W. Ryan Diver</name>
<affiliation><nlm:aff id="A11">Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA</nlm:aff>
</affiliation>
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<author><name sortKey="Gapstur, Susan M" sort="Gapstur, Susan M" uniqKey="Gapstur S" first="Susan M." last="Gapstur">Susan M. Gapstur</name>
<affiliation><nlm:aff id="A11">Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA</nlm:aff>
</affiliation>
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<author><name sortKey="Gaziano, J Michael" sort="Gaziano, J Michael" uniqKey="Gaziano J" first="J. Michael" last="Gaziano">J. Michael Gaziano</name>
<affiliation><nlm:aff id="A1">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A12">Department of Medicine, Harvard Medical School, Boston, MA, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A13">Division of Aging, Brigham and Women’s Hospital, Boston, MA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Giles, Graham G" sort="Giles, Graham G" uniqKey="Giles G" first="Graham G." last="Giles">Graham G. Giles</name>
<affiliation><nlm:aff id="A14">Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A15">Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Henderson, Brian" sort="Henderson, Brian" uniqKey="Henderson B" first="Brian" last="Henderson">Brian Henderson</name>
<affiliation><nlm:aff id="A16">Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hoover, Robert" sort="Hoover, Robert" uniqKey="Hoover R" first="Robert" last="Hoover">Robert Hoover</name>
<affiliation><nlm:aff id="A3">Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Johansson, Mattias" sort="Johansson, Mattias" uniqKey="Johansson M" first="Mattias" last="Johansson">Mattias Johansson</name>
<affiliation><nlm:aff id="A17">International Agency for Research on Cancer, Lyon, France</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A18">Department of Biobank Research, Umeå University, Umeå, Sweden</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Le Marchand, Loic" sort="Le Marchand, Loic" uniqKey="Le Marchand L" first="Loic" last="Le Marchand">Loic Le Marchand</name>
<affiliation><nlm:aff id="A19">Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ma, Jing" sort="Ma, Jing" uniqKey="Ma J" first="Jing" last="Ma">Jing Ma</name>
<affiliation><nlm:aff id="A1">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A5">Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Navarro, Carmen" sort="Navarro, Carmen" uniqKey="Navarro C" first="Carmen" last="Navarro">Carmen Navarro</name>
<affiliation><nlm:aff id="A20">Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A21">Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Overvad, Kim" sort="Overvad, Kim" uniqKey="Overvad K" first="Kim" last="Overvad">Kim Overvad</name>
<affiliation><nlm:aff id="A22">Department of Public Health, Aarhus University, Aarhus, Denmark</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Schumacher, Fredrick R" sort="Schumacher, Fredrick R" uniqKey="Schumacher F" first="Fredrick R." last="Schumacher">Fredrick R. Schumacher</name>
<affiliation><nlm:aff id="A16">Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Severi, Gianluca" sort="Severi, Gianluca" uniqKey="Severi G" first="Gianluca" last="Severi">Gianluca Severi</name>
<affiliation><nlm:aff id="A14">Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A23">HuGeF Foundation, Torino, Italy</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Siddiq, Afshan" sort="Siddiq, Afshan" uniqKey="Siddiq A" first="Afshan" last="Siddiq">Afshan Siddiq</name>
<affiliation><nlm:aff id="A24">Department of Genomics of Common Disease, Imperial College London, London, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Stampfer, Meir" sort="Stampfer, Meir" uniqKey="Stampfer M" first="Meir" last="Stampfer">Meir Stampfer</name>
<affiliation><nlm:aff id="A1">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A5">Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Stevens, Victoria L" sort="Stevens, Victoria L" uniqKey="Stevens V" first="Victoria L." last="Stevens">Victoria L. Stevens</name>
<affiliation><nlm:aff id="A11">Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Travis, Ruth C" sort="Travis, Ruth C" uniqKey="Travis R" first="Ruth C." last="Travis">Ruth C. Travis</name>
<affiliation><nlm:aff id="A25">Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Trichopoulos, Dimitrios" sort="Trichopoulos, Dimitrios" uniqKey="Trichopoulos D" first="Dimitrios" last="Trichopoulos">Dimitrios Trichopoulos</name>
<affiliation><nlm:aff id="A1">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A26">Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A27">Hellenic Health Foundation, Athens, Greece</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Vineis, Paolo" sort="Vineis, Paolo" uniqKey="Vineis P" first="Paolo" last="Vineis">Paolo Vineis</name>
<affiliation><nlm:aff id="A23">HuGeF Foundation, Torino, Italy</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A28">School of Public Health, Imperial College London, London, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mucci, Lorelei A" sort="Mucci, Lorelei A" uniqKey="Mucci L" first="Lorelei A." last="Mucci">Lorelei A. Mucci</name>
<affiliation><nlm:aff id="A1">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Yeager, Meredith" sort="Yeager, Meredith" uniqKey="Yeager M" first="Meredith" last="Yeager">Meredith Yeager</name>
<affiliation><nlm:aff id="A3">Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A9">Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Gaithersburg, MD, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Giovannucci, Edward" sort="Giovannucci, Edward" uniqKey="Giovannucci E" first="Edward" last="Giovannucci">Edward Giovannucci</name>
<affiliation><nlm:aff id="A1">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kraft, Peter" sort="Kraft, Peter" uniqKey="Kraft P" first="Peter" last="Kraft">Peter Kraft</name>
<affiliation><nlm:aff id="A1">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff>
</affiliation>
</author>
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<date when="2014">2014</date>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Prostate Cancer (PCa) Risk Variants and Risk of Fatal PCa in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium</title>
<author><name sortKey="Shui, Irene M" sort="Shui, Irene M" uniqKey="Shui I" first="Irene M." last="Shui">Irene M. Shui</name>
<affiliation><nlm:aff id="A1">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lindstrom, Sara" sort="Lindstrom, Sara" uniqKey="Lindstrom S" first="Sara" last="Lindström">Sara Lindström</name>
<affiliation><nlm:aff id="A1">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kibel, Adam S" sort="Kibel, Adam S" uniqKey="Kibel A" first="Adam S." last="Kibel">Adam S. Kibel</name>
<affiliation><nlm:aff id="A2">Department of Surgery, Division of Urology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Berndt, Sonja I" sort="Berndt, Sonja I" uniqKey="Berndt S" first="Sonja I." last="Berndt">Sonja I. Berndt</name>
<affiliation><nlm:aff id="A3">Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Campa, Daniele" sort="Campa, Daniele" uniqKey="Campa D" first="Daniele" last="Campa">Daniele Campa</name>
<affiliation><nlm:aff id="A4">Genomic Epidemiology Group, German Cancer Research Center (Deutsches Krebsforschungszentrum), Heidelberg, Germany</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gerke, Travis" sort="Gerke, Travis" uniqKey="Gerke T" first="Travis" last="Gerke">Travis Gerke</name>
<affiliation><nlm:aff id="A1">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Penney, Kathryn L" sort="Penney, Kathryn L" uniqKey="Penney K" first="Kathryn L." last="Penney">Kathryn L. Penney</name>
<affiliation><nlm:aff id="A1">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A5">Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Albanes, Demetrius" sort="Albanes, Demetrius" uniqKey="Albanes D" first="Demetrius" last="Albanes">Demetrius Albanes</name>
<affiliation><nlm:aff id="A3">Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Berg, Christine" sort="Berg, Christine" uniqKey="Berg C" first="Christine" last="Berg">Christine Berg</name>
<affiliation><nlm:aff id="A6">Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medicine, Baltimore, MD, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bueno De Mesquita, H Bas" sort="Bueno De Mesquita, H Bas" uniqKey="Bueno De Mesquita H" first="H. Bas" last="Bueno-De-Mesquita">H. Bas Bueno-De-Mesquita</name>
<affiliation><nlm:aff id="A7">National Institute for Public Health and the Environment, Bilthoven, The Netherlands</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A8">Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A28">School of Public Health, Imperial College London, London, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chanock, Stephen" sort="Chanock, Stephen" uniqKey="Chanock S" first="Stephen" last="Chanock">Stephen Chanock</name>
<affiliation><nlm:aff id="A3">Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A9">Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Gaithersburg, MD, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Crawford, E David" sort="Crawford, E David" uniqKey="Crawford E" first="E. David" last="Crawford">E. David Crawford</name>
<affiliation><nlm:aff id="A10">Urologic Oncology, University of Colorado, Denver, CO, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Diver, W Ryan" sort="Diver, W Ryan" uniqKey="Diver W" first="W. Ryan" last="Diver">W. Ryan Diver</name>
<affiliation><nlm:aff id="A11">Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gapstur, Susan M" sort="Gapstur, Susan M" uniqKey="Gapstur S" first="Susan M." last="Gapstur">Susan M. Gapstur</name>
<affiliation><nlm:aff id="A11">Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gaziano, J Michael" sort="Gaziano, J Michael" uniqKey="Gaziano J" first="J. Michael" last="Gaziano">J. Michael Gaziano</name>
<affiliation><nlm:aff id="A1">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A12">Department of Medicine, Harvard Medical School, Boston, MA, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A13">Division of Aging, Brigham and Women’s Hospital, Boston, MA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Giles, Graham G" sort="Giles, Graham G" uniqKey="Giles G" first="Graham G." last="Giles">Graham G. Giles</name>
<affiliation><nlm:aff id="A14">Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A15">Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Henderson, Brian" sort="Henderson, Brian" uniqKey="Henderson B" first="Brian" last="Henderson">Brian Henderson</name>
<affiliation><nlm:aff id="A16">Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hoover, Robert" sort="Hoover, Robert" uniqKey="Hoover R" first="Robert" last="Hoover">Robert Hoover</name>
<affiliation><nlm:aff id="A3">Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Johansson, Mattias" sort="Johansson, Mattias" uniqKey="Johansson M" first="Mattias" last="Johansson">Mattias Johansson</name>
<affiliation><nlm:aff id="A17">International Agency for Research on Cancer, Lyon, France</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A18">Department of Biobank Research, Umeå University, Umeå, Sweden</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Le Marchand, Loic" sort="Le Marchand, Loic" uniqKey="Le Marchand L" first="Loic" last="Le Marchand">Loic Le Marchand</name>
<affiliation><nlm:aff id="A19">Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ma, Jing" sort="Ma, Jing" uniqKey="Ma J" first="Jing" last="Ma">Jing Ma</name>
<affiliation><nlm:aff id="A1">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A5">Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Navarro, Carmen" sort="Navarro, Carmen" uniqKey="Navarro C" first="Carmen" last="Navarro">Carmen Navarro</name>
<affiliation><nlm:aff id="A20">Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A21">Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Overvad, Kim" sort="Overvad, Kim" uniqKey="Overvad K" first="Kim" last="Overvad">Kim Overvad</name>
<affiliation><nlm:aff id="A22">Department of Public Health, Aarhus University, Aarhus, Denmark</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Schumacher, Fredrick R" sort="Schumacher, Fredrick R" uniqKey="Schumacher F" first="Fredrick R." last="Schumacher">Fredrick R. Schumacher</name>
<affiliation><nlm:aff id="A16">Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Severi, Gianluca" sort="Severi, Gianluca" uniqKey="Severi G" first="Gianluca" last="Severi">Gianluca Severi</name>
<affiliation><nlm:aff id="A14">Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A23">HuGeF Foundation, Torino, Italy</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Siddiq, Afshan" sort="Siddiq, Afshan" uniqKey="Siddiq A" first="Afshan" last="Siddiq">Afshan Siddiq</name>
<affiliation><nlm:aff id="A24">Department of Genomics of Common Disease, Imperial College London, London, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Stampfer, Meir" sort="Stampfer, Meir" uniqKey="Stampfer M" first="Meir" last="Stampfer">Meir Stampfer</name>
<affiliation><nlm:aff id="A1">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A5">Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Stevens, Victoria L" sort="Stevens, Victoria L" uniqKey="Stevens V" first="Victoria L." last="Stevens">Victoria L. Stevens</name>
<affiliation><nlm:aff id="A11">Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Travis, Ruth C" sort="Travis, Ruth C" uniqKey="Travis R" first="Ruth C." last="Travis">Ruth C. Travis</name>
<affiliation><nlm:aff id="A25">Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Trichopoulos, Dimitrios" sort="Trichopoulos, Dimitrios" uniqKey="Trichopoulos D" first="Dimitrios" last="Trichopoulos">Dimitrios Trichopoulos</name>
<affiliation><nlm:aff id="A1">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A26">Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A27">Hellenic Health Foundation, Athens, Greece</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Vineis, Paolo" sort="Vineis, Paolo" uniqKey="Vineis P" first="Paolo" last="Vineis">Paolo Vineis</name>
<affiliation><nlm:aff id="A23">HuGeF Foundation, Torino, Italy</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A28">School of Public Health, Imperial College London, London, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mucci, Lorelei A" sort="Mucci, Lorelei A" uniqKey="Mucci L" first="Lorelei A." last="Mucci">Lorelei A. Mucci</name>
<affiliation><nlm:aff id="A1">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Yeager, Meredith" sort="Yeager, Meredith" uniqKey="Yeager M" first="Meredith" last="Yeager">Meredith Yeager</name>
<affiliation><nlm:aff id="A3">Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A9">Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Gaithersburg, MD, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Giovannucci, Edward" sort="Giovannucci, Edward" uniqKey="Giovannucci E" first="Edward" last="Giovannucci">Edward Giovannucci</name>
<affiliation><nlm:aff id="A1">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kraft, Peter" sort="Kraft, Peter" uniqKey="Kraft P" first="Peter" last="Kraft">Peter Kraft</name>
<affiliation><nlm:aff id="A1">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">European urology</title>
<idno type="ISSN">0302-2838</idno>
<idno type="eISSN">1873-7560</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title>
<p id="P1">Screening and diagnosis of prostate cancer (PCa) is hampered by an inability to predict who has the potential to develop fatal disease and who has indolent cancer. Studies have identified multiple genetic risk loci for PCa incidence, but it is unknown whether they could be used as biomarkers for PCa-specific mortality (PCSM).</p>
</sec>
<sec id="S2"><title>Objective</title>
<p id="P2">To examine the association of 47 established PCa risk single-nucleotide polymorphisms (SNPs) with PCSM.</p>
</sec>
<sec id="S3"><title>Design, setting, and participants</title>
<p id="P3">We included 10 487 men who had PCa and 11 024 controls, with a median follow-up of 8.3 yr, during which 1053 PCa deaths occurred.</p>
</sec>
<sec id="S4"><title>Outcome measurements and statistical analysis</title>
<p id="P4">The main outcome was PCSM. The <italic>risk allele</italic>
was defined as the allele associated with an increased risk for PCa in the literature. We used Cox proportional hazards regression to calculate the hazard ratios of each SNP with time to progression to PCSM after diagnosis. We also used logistic regression to calculate odds ratios for each risk SNP, comparing fatal PCa cases to controls.</p>
</sec>
<sec id="S5"><title>Results and limitations</title>
<p id="P5">Among the cases, we found that 8 of the 47 SNPs were significantly associated (<italic>p</italic>
< 0.05) with time to PCSM. The risk allele of rs11672691 (intergenic) was associated with an increased risk for PCSM, while 7 SNPs had risk alleles inversely associated (rs13385191 [<italic>C2orf43</italic>
], rs17021918 [<italic>PDLIM5</italic>
], rs10486567 [<italic>JAZF1</italic>
], rs6465657 [<italic>LMTK2</italic>
], rs7127900 (intergenic), rs2735839 [<italic>KLK3</italic>
], rs10993994 [<italic>MSMB</italic>
], rs13385191 [<italic>C2orf43</italic>
]). In the case-control analysis, 22 SNPs were associated (<italic>p</italic>
< 0.05) with the risk of fatal PCa, but most did not differentiate between fatal and nonfatal PCa. Rs11672691 and rs10993994 were associated with both fatal and nonfatal PCa, while rs6465657, rs7127900, rs2735839, and rs13385191 were associated with nonfatal PCa only.</p>
</sec>
<sec id="S6"><title>Conclusions</title>
<p id="P6">Eight established risk loci were associated with progression to PCSM after diagnosis. Twenty-two SNPs were associated with fatal PCa incidence, but most did not differentiate between fatal and nonfatal PCa. The relatively small magnitudes of the associations do not translate well into risk prediction, but these findings merit further follow-up, because they may yield important clues about the complex biology of fatal PCa. Patient summary: In this report, we assessed whether established PCa risk variants could predict PCSM. We found eight risk variants associated with PCSM: One predicted an increased risk of PCSM, while seven were associated with decreased risk. Larger studies that focus on fatal PCa are needed to identify more markers that could aid prediction.</p>
</sec>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">7512719</journal-id>
<journal-id journal-id-type="pubmed-jr-id">3630</journal-id>
<journal-id journal-id-type="nlm-ta">Eur Urol</journal-id>
<journal-id journal-id-type="iso-abbrev">Eur. Urol.</journal-id>
<journal-title-group><journal-title>European urology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0302-2838</issn>
<issn pub-type="epub">1873-7560</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">24411283</article-id>
<article-id pub-id-type="pmc">4006298</article-id>
<article-id pub-id-type="doi">10.1016/j.eururo.2013.12.058</article-id>
<article-id pub-id-type="manuscript">NIHMS554719</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Prostate Cancer (PCa) Risk Variants and Risk of Fatal PCa in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Shui</surname>
<given-names>Irene M.</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lindström</surname>
<given-names>Sara</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kibel</surname>
<given-names>Adam S.</given-names>
</name>
<xref ref-type="aff" rid="A2">b</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Berndt</surname>
<given-names>Sonja I.</given-names>
</name>
<xref ref-type="aff" rid="A3">c</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Campa</surname>
<given-names>Daniele</given-names>
</name>
<xref ref-type="aff" rid="A4">d</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gerke</surname>
<given-names>Travis</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Penney</surname>
<given-names>Kathryn L.</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
<xref ref-type="aff" rid="A5">e</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Albanes</surname>
<given-names>Demetrius</given-names>
</name>
<xref ref-type="aff" rid="A3">c</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Berg</surname>
<given-names>Christine</given-names>
</name>
<xref ref-type="aff" rid="A6">f</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bueno-de-Mesquita</surname>
<given-names>H. Bas</given-names>
</name>
<xref ref-type="aff" rid="A7">g</xref>
<xref ref-type="aff" rid="A8">h</xref>
<xref ref-type="aff" rid="A28">bb</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chanock</surname>
<given-names>Stephen</given-names>
</name>
<xref ref-type="aff" rid="A3">c</xref>
<xref ref-type="aff" rid="A9">i</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Crawford</surname>
<given-names>E. David</given-names>
</name>
<xref ref-type="aff" rid="A10">j</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Diver</surname>
<given-names>W. Ryan</given-names>
</name>
<xref ref-type="aff" rid="A11">k</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gapstur</surname>
<given-names>Susan M.</given-names>
</name>
<xref ref-type="aff" rid="A11">k</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gaziano</surname>
<given-names>J. Michael</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
<xref ref-type="aff" rid="A12">l</xref>
<xref ref-type="aff" rid="A13">m</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Giles</surname>
<given-names>Graham G.</given-names>
</name>
<xref ref-type="aff" rid="A14">n</xref>
<xref ref-type="aff" rid="A15">o</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Henderson</surname>
<given-names>Brian</given-names>
</name>
<xref ref-type="aff" rid="A16">p</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hoover</surname>
<given-names>Robert</given-names>
</name>
<xref ref-type="aff" rid="A3">c</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Johansson</surname>
<given-names>Mattias</given-names>
</name>
<xref ref-type="aff" rid="A17">q</xref>
<xref ref-type="aff" rid="A18">r</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Le Marchand</surname>
<given-names>Loic</given-names>
</name>
<xref ref-type="aff" rid="A19">s</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ma</surname>
<given-names>Jing</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
<xref ref-type="aff" rid="A5">e</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Navarro</surname>
<given-names>Carmen</given-names>
</name>
<xref ref-type="aff" rid="A20">t</xref>
<xref ref-type="aff" rid="A21">u</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Overvad</surname>
<given-names>Kim</given-names>
</name>
<xref ref-type="aff" rid="A22">v</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Schumacher</surname>
<given-names>Fredrick R.</given-names>
</name>
<xref ref-type="aff" rid="A16">p</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Severi</surname>
<given-names>Gianluca</given-names>
</name>
<xref ref-type="aff" rid="A14">n</xref>
<xref ref-type="aff" rid="A23">w</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Siddiq</surname>
<given-names>Afshan</given-names>
</name>
<xref ref-type="aff" rid="A24">x</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Stampfer</surname>
<given-names>Meir</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
<xref ref-type="aff" rid="A5">e</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Stevens</surname>
<given-names>Victoria L.</given-names>
</name>
<xref ref-type="aff" rid="A11">k</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Travis</surname>
<given-names>Ruth C.</given-names>
</name>
<xref ref-type="aff" rid="A25">y</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Trichopoulos</surname>
<given-names>Dimitrios</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
<xref ref-type="aff" rid="A26">z</xref>
<xref ref-type="aff" rid="A27">aa</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Vineis</surname>
<given-names>Paolo</given-names>
</name>
<xref ref-type="aff" rid="A23">w</xref>
<xref ref-type="aff" rid="A28">bb</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Mucci</surname>
<given-names>Lorelei A.</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Yeager</surname>
<given-names>Meredith</given-names>
</name>
<xref ref-type="aff" rid="A3">c</xref>
<xref ref-type="aff" rid="A9">i</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Giovannucci</surname>
<given-names>Edward</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kraft</surname>
<given-names>Peter</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>a</label>
Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</aff>
<aff id="A2"><label>b</label>
Department of Surgery, Division of Urology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA</aff>
<aff id="A3"><label>c</label>
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA</aff>
<aff id="A4"><label>d</label>
Genomic Epidemiology Group, German Cancer Research Center (Deutsches Krebsforschungszentrum), Heidelberg, Germany</aff>
<aff id="A5"><label>e</label>
Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA</aff>
<aff id="A6"><label>f</label>
Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medicine, Baltimore, MD, USA</aff>
<aff id="A7"><label>g</label>
National Institute for Public Health and the Environment, Bilthoven, The Netherlands</aff>
<aff id="A8"><label>h</label>
Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands</aff>
<aff id="A9"><label>i</label>
Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Gaithersburg, MD, USA</aff>
<aff id="A10"><label>j</label>
Urologic Oncology, University of Colorado, Denver, CO, USA</aff>
<aff id="A11"><label>k</label>
Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA</aff>
<aff id="A12"><label>l</label>
Department of Medicine, Harvard Medical School, Boston, MA, USA</aff>
<aff id="A13"><label>m</label>
Division of Aging, Brigham and Women’s Hospital, Boston, MA, USA</aff>
<aff id="A14"><label>n</label>
Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia</aff>
<aff id="A15"><label>o</label>
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia</aff>
<aff id="A16"><label>p</label>
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA</aff>
<aff id="A17"><label>q</label>
International Agency for Research on Cancer, Lyon, France</aff>
<aff id="A18"><label>r</label>
Department of Biobank Research, Umeå University, Umeå, Sweden</aff>
<aff id="A19"><label>s</label>
Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA</aff>
<aff id="A20"><label>t</label>
Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain</aff>
<aff id="A21"><label>u</label>
Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain</aff>
<aff id="A22"><label>v</label>
Department of Public Health, Aarhus University, Aarhus, Denmark</aff>
<aff id="A23"><label>w</label>
HuGeF Foundation, Torino, Italy</aff>
<aff id="A24"><label>x</label>
Department of Genomics of Common Disease, Imperial College London, London, United Kingdom</aff>
<aff id="A25"><label>y</label>
Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom</aff>
<aff id="A26"><label>z</label>
Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece</aff>
<aff id="A27"><label>aa</label>
Hellenic Health Foundation, Athens, Greece</aff>
<aff id="A28"><label>bb</label>
School of Public Health, Imperial College London, London, United Kingdom</aff>
<author-notes><corresp id="cor1"><label>*</label>
Corresponding author. Harvard School of Public Health, Department of Epidemiology, 677 Huntington Ave, Boston, MA 02115 USA. Tel.: +1 617 432 2916; Fax: +1 617 566 7805. <email>ishui@hsph.harvard.edu</email>
(I. Shui)</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>21</day>
<month>2</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="epub"><day>04</day>
<month>1</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="ppub"><month>6</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>01</day>
<month>6</month>
<year>2015</year>
</pub-date>
<volume>65</volume>
<issue>6</issue>
<fpage>1069</fpage>
<lpage>1075</lpage>
<pmc-comment>elocation-id from pubmed: 10.1016/j.eururo.2013.12.058</pmc-comment>
<permissions><copyright-statement>© 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.</copyright-statement>
<copyright-year>2013</copyright-year>
</permissions>
<abstract><sec id="S1"><title>Background</title>
<p id="P1">Screening and diagnosis of prostate cancer (PCa) is hampered by an inability to predict who has the potential to develop fatal disease and who has indolent cancer. Studies have identified multiple genetic risk loci for PCa incidence, but it is unknown whether they could be used as biomarkers for PCa-specific mortality (PCSM).</p>
</sec>
<sec id="S2"><title>Objective</title>
<p id="P2">To examine the association of 47 established PCa risk single-nucleotide polymorphisms (SNPs) with PCSM.</p>
</sec>
<sec id="S3"><title>Design, setting, and participants</title>
<p id="P3">We included 10 487 men who had PCa and 11 024 controls, with a median follow-up of 8.3 yr, during which 1053 PCa deaths occurred.</p>
</sec>
<sec id="S4"><title>Outcome measurements and statistical analysis</title>
<p id="P4">The main outcome was PCSM. The <italic>risk allele</italic>
was defined as the allele associated with an increased risk for PCa in the literature. We used Cox proportional hazards regression to calculate the hazard ratios of each SNP with time to progression to PCSM after diagnosis. We also used logistic regression to calculate odds ratios for each risk SNP, comparing fatal PCa cases to controls.</p>
</sec>
<sec id="S5"><title>Results and limitations</title>
<p id="P5">Among the cases, we found that 8 of the 47 SNPs were significantly associated (<italic>p</italic>
< 0.05) with time to PCSM. The risk allele of rs11672691 (intergenic) was associated with an increased risk for PCSM, while 7 SNPs had risk alleles inversely associated (rs13385191 [<italic>C2orf43</italic>
], rs17021918 [<italic>PDLIM5</italic>
], rs10486567 [<italic>JAZF1</italic>
], rs6465657 [<italic>LMTK2</italic>
], rs7127900 (intergenic), rs2735839 [<italic>KLK3</italic>
], rs10993994 [<italic>MSMB</italic>
], rs13385191 [<italic>C2orf43</italic>
]). In the case-control analysis, 22 SNPs were associated (<italic>p</italic>
< 0.05) with the risk of fatal PCa, but most did not differentiate between fatal and nonfatal PCa. Rs11672691 and rs10993994 were associated with both fatal and nonfatal PCa, while rs6465657, rs7127900, rs2735839, and rs13385191 were associated with nonfatal PCa only.</p>
</sec>
<sec id="S6"><title>Conclusions</title>
<p id="P6">Eight established risk loci were associated with progression to PCSM after diagnosis. Twenty-two SNPs were associated with fatal PCa incidence, but most did not differentiate between fatal and nonfatal PCa. The relatively small magnitudes of the associations do not translate well into risk prediction, but these findings merit further follow-up, because they may yield important clues about the complex biology of fatal PCa. Patient summary: In this report, we assessed whether established PCa risk variants could predict PCSM. We found eight risk variants associated with PCSM: One predicted an increased risk of PCSM, while seven were associated with decreased risk. Larger studies that focus on fatal PCa are needed to identify more markers that could aid prediction.</p>
</sec>
</abstract>
<kwd-group><kwd>Prostate cancer</kwd>
<kwd>Risk single nucleotide polymorphisms</kwd>
<kwd>Prostate cancer mortality</kwd>
<kwd>Genetic epidemiology</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>
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