Common genetic variants in prostate cancer risk prediction – Results from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3)
Identifieur interne : 002086 ( Pmc/Corpus ); précédent : 002085; suivant : 002087Common genetic variants in prostate cancer risk prediction – Results from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3)
Auteurs : Sara Lindström ; Fredrick R. Schumacher ; David Cox ; Ruth C. Travis ; Demetrius Albanes ; Naomi E. Allen ; Gerald Andriole ; Sonja I. Berndt ; Heiner Boeing ; H. Bas Bueno-De-Mesquita ; E. David Crawford ; W. Ryan Diver ; J. Michael Ganziano ; Graham G. Giles ; Edward Giovannucci ; Carlos A. Gonzalez ; Brian Henderson ; David J. Hunter ; Mattias Johansson ; Laurence N. Kolonel ; Jing Ma ; Loic Le Marchand ; Valeria Pala ; Meir Stampfer ; Daniel O. Stram ; Michael J. Thun ; Anne Tjonneland ; Dimitrios Trichopoulos ; Jarmo Virtamo ; Stephanie J. Weinstein ; Walter C. Willett ; Meredith Yeager ; Richard B. Hayes ; Gianluca Severi ; Christopher A. Haiman ; Stephen J. Chanock ; Peter KraftSource :
- Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology [ 1055-9965 ] ; 2012.
Abstract
One of the goals of personalized medicine is to generate individual risk profiles that could identify individuals in the population that exhibit high risk. The discovery of more than two-dozen independent SNP markers in prostate cancer has raised the possibility for such risk stratification. In this study, we evaluated the discriminative and predictive ability for prostate cancer risk models incorporating 25 common prostate cancer genetic markers, family history of prostate cancer and age.
We fit a series of risk models and estimated their performance in 7,509 prostate cancer cases and 7,652 controls within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). We also calculated absolute risks based on SEER incidence data.
The best risk model (C-statistic=0.642) included individual genetic markers and family history of prostate cancer. We observed a decreasing trend in discriminative ability with advancing age (
Our results indicate that incorporating genetic information and family history in prostate cancer risk models can be particularly useful for identifying younger men that might benefit from PSA screening.
Although adding genetic risk markers improves model performance, the clinical utility of these genetic risk models is limited.
Url:
DOI: 10.1158/1055-9965.EPI-11-1038
PubMed: 22237985
PubMed Central: 3318963
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PMC:3318963Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Common genetic variants in prostate cancer risk prediction – Results from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3)</title><author><name sortKey="Lindstrom, Sara" sort="Lindstrom, Sara" uniqKey="Lindstrom S" first="Sara" last="Lindström">Sara Lindström</name><affiliation><nlm:aff id="A1">Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</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="A3">Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Cox, David" sort="Cox, David" uniqKey="Cox D" first="David" last="Cox">David Cox</name><affiliation><nlm:aff id="A4">Cancer Research Center of Lyon, Centre Léon Bérard, INSERM U1052, Lyon, France</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Department of Medicine and Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom</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="A6">Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom</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="A7">Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Allen, Naomi E" sort="Allen, Naomi E" uniqKey="Allen N" first="Naomi E." last="Allen">Naomi E. Allen</name><affiliation><nlm:aff id="A6">Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Andriole, Gerald" sort="Andriole, Gerald" uniqKey="Andriole G" first="Gerald" last="Andriole">Gerald Andriole</name><affiliation><nlm:aff id="A8">Division of Urologic Surgery, Washington University School of Medicine, St Louis, MO, 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="A7">Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Boeing, Heiner" sort="Boeing, Heiner" uniqKey="Boeing H" first="Heiner" last="Boeing">Heiner Boeing</name><affiliation><nlm:aff id="A9">Department of Epidemiology, Deutsches Institut für Ernährungsforschung, Potsdam-Rehbrücke, Germany</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="A10">National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A11">Department of Gastroenterology and Hepatology, University Medical Centre Utrecht (UMCU), Utrecht, The Netherlands</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="A12">Urologic Oncology, University of Colorado Health Sciences Center, 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="A13">Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA</nlm:aff></affiliation></author><author><name sortKey="Ganziano, J Michael" sort="Ganziano, J Michael" uniqKey="Ganziano J" first="J. Michael" last="Ganziano">J. Michael Ganziano</name><affiliation><nlm:aff id="A14">Massachusetts Veterans Epidemiology and Research Information Center (MAVERIC) and Geriatric Research, Education, and Clinical Center (GRECC), Boston Veterans Affairs Healthcare System, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A15">Division of Aging, Department of Medicine, 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="A16">Cancer Epidemiology Centre, Cancer Council Victoria and the Centre for Molecular, Genetic, Environmental, and Analytic Epidemiology, University of Melbourne, Melbourne, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A17">Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia</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="A2">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A18">Department of Nutrition, Harvard School of Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A20">Department of Medicine, Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Gonzalez, Carlos A" sort="Gonzalez, Carlos A" uniqKey="Gonzalez C" first="Carlos A." last="Gonzalez">Carlos A. Gonzalez</name><affiliation><nlm:aff id="A19">Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology (IDIBELL, RETICC -RD06/0020), Barcelona, Spain</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="A3">Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Hunter, David J" sort="Hunter, David J" uniqKey="Hunter D" first="David J." last="Hunter">David J. Hunter</name><affiliation><nlm:aff id="A1">Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A20">Department of Medicine, Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, 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="A21">International Agency for Research on Cancer, Lyon, France</nlm:aff></affiliation><affiliation><nlm:aff id="A22">Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Sweden</nlm:aff></affiliation></author><author><name sortKey="Kolonel, Laurence N" sort="Kolonel, Laurence N" uniqKey="Kolonel L" first="Laurence N." last="Kolonel">Laurence N. Kolonel</name><affiliation><nlm:aff id="A23">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="A20">Department of Medicine, Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA</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="A23">Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA</nlm:aff></affiliation></author><author><name sortKey="Pala, Valeria" sort="Pala, Valeria" uniqKey="Pala V" first="Valeria" last="Pala">Valeria Pala</name><affiliation><nlm:aff id="A24">Department of Predictive Medicine, Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy</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="A2">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A18">Department of Nutrition, Harvard School of Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A20">Department of Medicine, Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Stram, Daniel O" sort="Stram, Daniel O" uniqKey="Stram D" first="Daniel O." last="Stram">Daniel O. Stram</name><affiliation><nlm:aff id="A3">Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Thun, Michael J" sort="Thun, Michael J" uniqKey="Thun M" first="Michael J." last="Thun">Michael J. Thun</name><affiliation><nlm:aff id="A13">Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA</nlm:aff></affiliation></author><author><name sortKey="Tjonneland, Anne" sort="Tjonneland, Anne" uniqKey="Tjonneland A" first="Anne" last="Tjonneland">Anne Tjonneland</name><affiliation><nlm:aff id="A25">Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark</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="A2">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, Greece</nlm:aff></affiliation></author><author><name sortKey="Virtamo, Jarmo" sort="Virtamo, Jarmo" uniqKey="Virtamo J" first="Jarmo" last="Virtamo">Jarmo Virtamo</name><affiliation><nlm:aff id="A27">Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Weinstein, Stephanie J" sort="Weinstein, Stephanie J" uniqKey="Weinstein S" first="Stephanie J." last="Weinstein">Stephanie J. Weinstein</name><affiliation><nlm:aff id="A7">Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Willett, Walter C" sort="Willett, Walter C" uniqKey="Willett W" first="Walter C." last="Willett">Walter C. Willett</name><affiliation><nlm:aff id="A18">Department of Nutrition, 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="A7">Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Hayes, Richard B" sort="Hayes, Richard B" uniqKey="Hayes R" first="Richard B." last="Hayes">Richard B. Hayes</name><affiliation><nlm:aff id="A28">Division of Epidemiology, NYU Langone Medical Center, New York, NY, 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="A16">Cancer Epidemiology Centre, Cancer Council Victoria and the Centre for Molecular, Genetic, Environmental, and Analytic Epidemiology, University of Melbourne, Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Haiman, Christopher A" sort="Haiman, Christopher A" uniqKey="Haiman C" first="Christopher A." last="Haiman">Christopher A. Haiman</name><affiliation><nlm:aff id="A3">Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Chanock, Stephen J" sort="Chanock, Stephen J" uniqKey="Chanock S" first="Stephen J." last="Chanock">Stephen J. Chanock</name><affiliation><nlm:aff id="A7">Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 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">Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A29">Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22237985</idno><idno type="pmc">3318963</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3318963</idno><idno type="RBID">PMC:3318963</idno><idno type="doi">10.1158/1055-9965.EPI-11-1038</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">002086</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002086</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Common genetic variants in prostate cancer risk prediction – Results from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3)</title><author><name sortKey="Lindstrom, Sara" sort="Lindstrom, Sara" uniqKey="Lindstrom S" first="Sara" last="Lindström">Sara Lindström</name><affiliation><nlm:aff id="A1">Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</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="A3">Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Cox, David" sort="Cox, David" uniqKey="Cox D" first="David" last="Cox">David Cox</name><affiliation><nlm:aff id="A4">Cancer Research Center of Lyon, Centre Léon Bérard, INSERM U1052, Lyon, France</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Department of Medicine and Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom</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="A6">Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom</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="A7">Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Allen, Naomi E" sort="Allen, Naomi E" uniqKey="Allen N" first="Naomi E." last="Allen">Naomi E. Allen</name><affiliation><nlm:aff id="A6">Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Andriole, Gerald" sort="Andriole, Gerald" uniqKey="Andriole G" first="Gerald" last="Andriole">Gerald Andriole</name><affiliation><nlm:aff id="A8">Division of Urologic Surgery, Washington University School of Medicine, St Louis, MO, 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="A7">Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Boeing, Heiner" sort="Boeing, Heiner" uniqKey="Boeing H" first="Heiner" last="Boeing">Heiner Boeing</name><affiliation><nlm:aff id="A9">Department of Epidemiology, Deutsches Institut für Ernährungsforschung, Potsdam-Rehbrücke, Germany</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="A10">National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A11">Department of Gastroenterology and Hepatology, University Medical Centre Utrecht (UMCU), Utrecht, The Netherlands</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="A12">Urologic Oncology, University of Colorado Health Sciences Center, 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="A13">Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA</nlm:aff></affiliation></author><author><name sortKey="Ganziano, J Michael" sort="Ganziano, J Michael" uniqKey="Ganziano J" first="J. Michael" last="Ganziano">J. Michael Ganziano</name><affiliation><nlm:aff id="A14">Massachusetts Veterans Epidemiology and Research Information Center (MAVERIC) and Geriatric Research, Education, and Clinical Center (GRECC), Boston Veterans Affairs Healthcare System, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A15">Division of Aging, Department of Medicine, 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="A16">Cancer Epidemiology Centre, Cancer Council Victoria and the Centre for Molecular, Genetic, Environmental, and Analytic Epidemiology, University of Melbourne, Melbourne, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A17">Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia</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="A2">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A18">Department of Nutrition, Harvard School of Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A20">Department of Medicine, Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Gonzalez, Carlos A" sort="Gonzalez, Carlos A" uniqKey="Gonzalez C" first="Carlos A." last="Gonzalez">Carlos A. Gonzalez</name><affiliation><nlm:aff id="A19">Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology (IDIBELL, RETICC -RD06/0020), Barcelona, Spain</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="A3">Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Hunter, David J" sort="Hunter, David J" uniqKey="Hunter D" first="David J." last="Hunter">David J. Hunter</name><affiliation><nlm:aff id="A1">Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A20">Department of Medicine, Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, 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="A21">International Agency for Research on Cancer, Lyon, France</nlm:aff></affiliation><affiliation><nlm:aff id="A22">Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Sweden</nlm:aff></affiliation></author><author><name sortKey="Kolonel, Laurence N" sort="Kolonel, Laurence N" uniqKey="Kolonel L" first="Laurence N." last="Kolonel">Laurence N. Kolonel</name><affiliation><nlm:aff id="A23">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="A20">Department of Medicine, Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA</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="A23">Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA</nlm:aff></affiliation></author><author><name sortKey="Pala, Valeria" sort="Pala, Valeria" uniqKey="Pala V" first="Valeria" last="Pala">Valeria Pala</name><affiliation><nlm:aff id="A24">Department of Predictive Medicine, Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy</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="A2">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A18">Department of Nutrition, Harvard School of Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A20">Department of Medicine, Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Stram, Daniel O" sort="Stram, Daniel O" uniqKey="Stram D" first="Daniel O." last="Stram">Daniel O. Stram</name><affiliation><nlm:aff id="A3">Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Thun, Michael J" sort="Thun, Michael J" uniqKey="Thun M" first="Michael J." last="Thun">Michael J. Thun</name><affiliation><nlm:aff id="A13">Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA</nlm:aff></affiliation></author><author><name sortKey="Tjonneland, Anne" sort="Tjonneland, Anne" uniqKey="Tjonneland A" first="Anne" last="Tjonneland">Anne Tjonneland</name><affiliation><nlm:aff id="A25">Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark</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="A2">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, Greece</nlm:aff></affiliation></author><author><name sortKey="Virtamo, Jarmo" sort="Virtamo, Jarmo" uniqKey="Virtamo J" first="Jarmo" last="Virtamo">Jarmo Virtamo</name><affiliation><nlm:aff id="A27">Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Weinstein, Stephanie J" sort="Weinstein, Stephanie J" uniqKey="Weinstein S" first="Stephanie J." last="Weinstein">Stephanie J. Weinstein</name><affiliation><nlm:aff id="A7">Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Willett, Walter C" sort="Willett, Walter C" uniqKey="Willett W" first="Walter C." last="Willett">Walter C. Willett</name><affiliation><nlm:aff id="A18">Department of Nutrition, 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="A7">Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Hayes, Richard B" sort="Hayes, Richard B" uniqKey="Hayes R" first="Richard B." last="Hayes">Richard B. Hayes</name><affiliation><nlm:aff id="A28">Division of Epidemiology, NYU Langone Medical Center, New York, NY, 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="A16">Cancer Epidemiology Centre, Cancer Council Victoria and the Centre for Molecular, Genetic, Environmental, and Analytic Epidemiology, University of Melbourne, Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Haiman, Christopher A" sort="Haiman, Christopher A" uniqKey="Haiman C" first="Christopher A." last="Haiman">Christopher A. Haiman</name><affiliation><nlm:aff id="A3">Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Chanock, Stephen J" sort="Chanock, Stephen J" uniqKey="Chanock S" first="Stephen J." last="Chanock">Stephen J. Chanock</name><affiliation><nlm:aff id="A7">Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 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">Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A29">Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA</nlm:aff></affiliation></author></analytic><series><title level="j">Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology</title><idno type="ISSN">1055-9965</idno><idno type="eISSN">1538-7755</idno><imprint><date when="2012">2012</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">One of the goals of personalized medicine is to generate individual risk profiles that could identify individuals in the population that exhibit high risk. The discovery of more than two-dozen independent SNP markers in prostate cancer has raised the possibility for such risk stratification. In this study, we evaluated the discriminative and predictive ability for prostate cancer risk models incorporating 25 common prostate cancer genetic markers, family history of prostate cancer and age.</p></sec><sec id="S2"><title>Methods</title><p id="P2">We fit a series of risk models and estimated their performance in 7,509 prostate cancer cases and 7,652 controls within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). We also calculated absolute risks based on SEER incidence data.</p></sec><sec id="S3"><title>Results</title><p id="P3">The best risk model (C-statistic=0.642) included individual genetic markers and family history of prostate cancer. We observed a decreasing trend in discriminative ability with advancing age (<italic>P</italic>=0.009), with highest accuracy in men younger than 60 years (C-statistic=0.679). The absolute ten-year risk for 50-year old men with a family history ranged from 1.6% (10<sup>th</sup> percentile of genetic risk) to 6.7% (90<sup>th</sup> percentile of genetic risk). For men without family history, the risk ranged from 0.8% (10<sup>th</sup> percentile) to 3.4% (90<sup>th</sup> percentile).</p></sec><sec id="S4"><title>Conclusions</title><p id="P4">Our results indicate that incorporating genetic information and family history in prostate cancer risk models can be particularly useful for identifying younger men that might benefit from PSA screening.</p></sec><sec id="S5"><title>Impact</title><p id="P5">Although adding genetic risk markers improves model performance, the clinical utility of these genetic risk models is limited.</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">9200608</journal-id><journal-id journal-id-type="pubmed-jr-id">2299</journal-id><journal-id journal-id-type="nlm-ta">Cancer Epidemiol Biomarkers Prev</journal-id><journal-id journal-id-type="iso-abbrev">Cancer Epidemiol. Biomarkers Prev.</journal-id><journal-title-group><journal-title>Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology</journal-title></journal-title-group><issn pub-type="ppub">1055-9965</issn><issn pub-type="epub">1538-7755</issn></journal-meta><article-meta><article-id pub-id-type="pmid">22237985</article-id><article-id pub-id-type="pmc">3318963</article-id><article-id pub-id-type="doi">10.1158/1055-9965.EPI-11-1038</article-id><article-id pub-id-type="manuscript">NIHMS349027</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Common genetic variants in prostate cancer risk prediction – Results from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3)</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Lindström</surname><given-names>Sara</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Schumacher</surname><given-names>Fredrick R.</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Cox</surname><given-names>David</given-names></name><xref ref-type="aff" rid="A4">4</xref><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Travis</surname><given-names>Ruth C.</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Albanes</surname><given-names>Demetrius</given-names></name><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Allen</surname><given-names>Naomi E.</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Andriole</surname><given-names>Gerald</given-names></name><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Berndt</surname><given-names>Sonja I.</given-names></name><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Boeing</surname><given-names>Heiner</given-names></name><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Bueno-de-Mesquita</surname><given-names>H. Bas</given-names></name><xref ref-type="aff" rid="A10">10</xref><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>Crawford</surname><given-names>E. David</given-names></name><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>Diver</surname><given-names>W. Ryan</given-names></name><xref ref-type="aff" rid="A13">13</xref></contrib><contrib contrib-type="author"><name><surname>Ganziano</surname><given-names>J. Michael</given-names></name><xref ref-type="aff" rid="A14">14</xref><xref ref-type="aff" rid="A15">15</xref></contrib><contrib contrib-type="author"><name><surname>Giles</surname><given-names>Graham G.</given-names></name><xref ref-type="aff" rid="A16">16</xref><xref ref-type="aff" rid="A17">17</xref></contrib><contrib contrib-type="author"><name><surname>Giovannucci</surname><given-names>Edward</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A18">18</xref><xref ref-type="aff" rid="A20">20</xref></contrib><contrib contrib-type="author"><name><surname>Gonzalez</surname><given-names>Carlos A.</given-names></name><xref ref-type="aff" rid="A19">19</xref></contrib><contrib contrib-type="author"><name><surname>Henderson</surname><given-names>Brian</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Hunter</surname><given-names>David J.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A20">20</xref></contrib><contrib contrib-type="author"><name><surname>Johansson</surname><given-names>Mattias</given-names></name><xref ref-type="aff" rid="A21">21</xref><xref ref-type="aff" rid="A22">22</xref></contrib><contrib contrib-type="author"><name><surname>Kolonel</surname><given-names>Laurence N.</given-names></name><xref ref-type="aff" rid="A23">23</xref></contrib><contrib contrib-type="author"><name><surname>Ma</surname><given-names>Jing</given-names></name><xref ref-type="aff" rid="A20">20</xref></contrib><contrib contrib-type="author"><name><surname>Le Marchand</surname><given-names>Loic</given-names></name><xref ref-type="aff" rid="A23">23</xref></contrib><contrib contrib-type="author"><name><surname>Pala</surname><given-names>Valeria</given-names></name><xref ref-type="aff" rid="A24">24</xref></contrib><contrib contrib-type="author"><name><surname>Stampfer</surname><given-names>Meir</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A18">18</xref><xref ref-type="aff" rid="A20">20</xref></contrib><contrib contrib-type="author"><name><surname>Stram</surname><given-names>Daniel O.</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Thun</surname><given-names>Michael J.</given-names></name><xref ref-type="aff" rid="A13">13</xref></contrib><contrib contrib-type="author"><name><surname>Tjonneland</surname><given-names>Anne</given-names></name><xref ref-type="aff" rid="A25">25</xref></contrib><contrib contrib-type="author"><name><surname>Trichopoulos</surname><given-names>Dimitrios</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A26">26</xref></contrib><contrib contrib-type="author"><name><surname>Virtamo</surname><given-names>Jarmo</given-names></name><xref ref-type="aff" rid="A27">27</xref></contrib><contrib contrib-type="author"><name><surname>Weinstein</surname><given-names>Stephanie J.</given-names></name><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Willett</surname><given-names>Walter C.</given-names></name><xref ref-type="aff" rid="A18">18</xref></contrib><contrib contrib-type="author"><name><surname>Yeager</surname><given-names>Meredith</given-names></name><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Hayes</surname><given-names>Richard B.</given-names></name><xref ref-type="aff" rid="A28">28</xref></contrib><contrib contrib-type="author"><name><surname>Severi</surname><given-names>Gianluca</given-names></name><xref ref-type="aff" rid="A16">16</xref></contrib><contrib contrib-type="author"><name><surname>Haiman</surname><given-names>Christopher A.</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Chanock</surname><given-names>Stephen J.</given-names></name><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Kraft</surname><given-names>Peter</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A29">29</xref></contrib></contrib-group><aff id="A1"><label>1</label>Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, MA, USA</aff><aff id="A2"><label>2</label>Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</aff><aff id="A3"><label>3</label>Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA</aff><aff id="A4"><label>4</label>Cancer Research Center of Lyon, Centre Léon Bérard, INSERM U1052, Lyon, France</aff><aff id="A5"><label>5</label>Department of Medicine and Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom</aff><aff id="A6"><label>6</label>Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom</aff><aff id="A7"><label>7</label>Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA</aff><aff id="A8"><label>8</label>Division of Urologic Surgery, Washington University School of Medicine, St Louis, MO, USA</aff><aff id="A9"><label>9</label>Department of Epidemiology, Deutsches Institut für Ernährungsforschung, Potsdam-Rehbrücke, Germany</aff><aff id="A10"><label>10</label>National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands</aff><aff id="A11"><label>11</label>Department of Gastroenterology and Hepatology, University Medical Centre Utrecht (UMCU), Utrecht, The Netherlands</aff><aff id="A12"><label>12</label>Urologic Oncology, University of Colorado Health Sciences Center, Denver, CO, USA</aff><aff id="A13"><label>13</label>Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA</aff><aff id="A14"><label>14</label>Massachusetts Veterans Epidemiology and Research Information Center (MAVERIC) and Geriatric Research, Education, and Clinical Center (GRECC), Boston Veterans Affairs Healthcare System, Boston, MA, USA</aff><aff id="A15"><label>15</label>Division of Aging, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA</aff><aff id="A16"><label>16</label>Cancer Epidemiology Centre, Cancer Council Victoria and the Centre for Molecular, Genetic, Environmental, and Analytic Epidemiology, University of Melbourne, Melbourne, Australia</aff><aff id="A17"><label>17</label>Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia</aff><aff id="A18"><label>18</label>Department of Nutrition, Harvard School of Public Health, Boston, MA, USA</aff><aff id="A19"><label>19</label>Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology (IDIBELL, RETICC -RD06/0020), Barcelona, Spain</aff><aff id="A20"><label>20</label>Department of Medicine, Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA</aff><aff id="A21"><label>21</label>International Agency for Research on Cancer, Lyon, France</aff><aff id="A22"><label>22</label>Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Sweden</aff><aff id="A23"><label>23</label>Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA</aff><aff id="A24"><label>24</label>Department of Predictive Medicine, Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy</aff><aff id="A25"><label>25</label>Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark</aff><aff id="A26"><label>26</label>Bureau of Epidemiologic Research, Academy of Athens, Greece</aff><aff id="A27"><label>27</label>Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland</aff><aff id="A28"><label>28</label>Division of Epidemiology, NYU Langone Medical Center, New York, NY, USA</aff><aff id="A29"><label>29</label>Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA</aff><author-notes><corresp id="FN1">Corresponding author: Peter Kraft, Department of Epidemiology, Department of Biostatistics, 655 Huntington Avenue, Building II Room 207, Boston, Massachusetts 02115, Phone: 617.432.4271, <email>pkraft@hsph.harvard.edu</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>12</day><month>3</month><year>2012</year></pub-date><pub-date pub-type="epub"><day>11</day><month>1</month><year>2012</year></pub-date><pub-date pub-type="ppub"><month>3</month><year>2012</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>3</month><year>2013</year></pub-date><volume>21</volume><issue>3</issue><fpage>437</fpage><lpage>444</lpage><abstract><sec id="S1"><title>Background</title><p id="P1">One of the goals of personalized medicine is to generate individual risk profiles that could identify individuals in the population that exhibit high risk. The discovery of more than two-dozen independent SNP markers in prostate cancer has raised the possibility for such risk stratification. In this study, we evaluated the discriminative and predictive ability for prostate cancer risk models incorporating 25 common prostate cancer genetic markers, family history of prostate cancer and age.</p></sec><sec id="S2"><title>Methods</title><p id="P2">We fit a series of risk models and estimated their performance in 7,509 prostate cancer cases and 7,652 controls within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). We also calculated absolute risks based on SEER incidence data.</p></sec><sec id="S3"><title>Results</title><p id="P3">The best risk model (C-statistic=0.642) included individual genetic markers and family history of prostate cancer. We observed a decreasing trend in discriminative ability with advancing age (<italic>P</italic>=0.009), with highest accuracy in men younger than 60 years (C-statistic=0.679). The absolute ten-year risk for 50-year old men with a family history ranged from 1.6% (10<sup>th</sup> percentile of genetic risk) to 6.7% (90<sup>th</sup> percentile of genetic risk). For men without family history, the risk ranged from 0.8% (10<sup>th</sup> percentile) to 3.4% (90<sup>th</sup> percentile).</p></sec><sec id="S4"><title>Conclusions</title><p id="P4">Our results indicate that incorporating genetic information and family history in prostate cancer risk models can be particularly useful for identifying younger men that might benefit from PSA screening.</p></sec><sec id="S5"><title>Impact</title><p id="P5">Although adding genetic risk markers improves model performance, the clinical utility of these genetic risk models is limited.</p></sec></abstract><kwd-group><kwd>Prostate cancer</kwd><kwd>polymorphism</kwd><kwd>risk prediction model</kwd></kwd-group><funding-group><award-group><funding-source country="United States">National Cancer Institute : NCI</funding-source><award-id>U01 CA098758-07 || CA</award-id></award-group><award-group><funding-source country="United States">National Cancer Institute : NCI</funding-source><award-id>U01 CA098710-06 || CA</award-id></award-group><award-group><funding-source country="United States">National Cancer Institute : NCI</funding-source><award-id>U01 CA098233-07 || CA</award-id></award-group><award-group><funding-source country="United States">National Cancer Institute : NCI</funding-source><award-id>U01 CA098216-06 || CA</award-id></award-group><award-group><funding-source country="United States">National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK</funding-source><award-id>R21 DK084529-02 || DK</award-id></award-group></funding-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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