Genome-wide association study of prostate cancer-specific survival

Robert Szulkin¹, Robert Karlsson², Thomas Whitington², Markus Aly², Henrik Gronberg², Rosalind A Eeles³, Douglas F Easton⁴, Zsofia Kote-Jarai⁵, Ali Amin Al Olama⁴, Sara Benlloch⁴, Kenneth Muir⁶, Graham G Giles⁷, Melissa C Southey⁸, Liesel M FitzGerald⁹, Brian E Henderson¹⁰, Fredrick R Schumacher¹⁰, Christopher A Haiman¹⁰, Csilla Sipeky¹¹, Teuvo L J Tammela¹², Børge G Nordestgaard¹³, Timothy J Key¹⁴, Ruth C Travis¹⁴, David E Neal¹⁵, Jenny L Donovan¹⁶, Freddie C Hamdy¹⁷, Paul D P Pharoah¹⁸, Nora Pashayan¹⁹, Kay-Tee Khaw²⁰, Janet L Stanford²¹, Stephen N Thibodeau²², Shannon K McDonnell²², Daniel J Schaid²², Christiane Maier²³, Walther Vogel²⁴, Manuel Luedeke²³, Kathleen Herkommer²⁵, Adam S Kibel²⁶, Cezary Cybulski²⁷, Jan Lubiński²⁷, Wojciech Kluźniak²⁷, Lisa Cannon-Albright²⁸, Hermann Brenner²⁹, Volker Herrmann³⁰, Bernd Holleczek³¹, Jong Y Park³², Thomas A Sellers³², Hui-Yi Lim³³, Chavdar Slavov³⁴, Radka P Kaneva³⁵, Vanio I Mitev³⁵, Amanda Spurdle³⁶, Manuel R Teixeira³⁷, Paula Paulo³⁸, Sofia Maia³⁸, Hardev Pandha³⁹, Agnieszka Michael³⁹, Andrzej Kierzek³⁹; PRACTICAL consortium; Jyotsna Batra⁴⁰, Judith A Clements⁴⁰; Australian Prostate Cancer BioResource; Demetrius Albanes⁴¹, Gerald L Andriole⁴², Sonja I Berndt⁴¹, Stephen Chanock⁴³, Susan M Gapstur⁴⁴, Edward L Giovannucci⁴⁵, David J Hunter⁴⁶, Peter Kraft⁴⁶, Loic Le Marchand⁴⁷, Jing Ma⁴⁸, Alison M Mondul⁴¹, Kathryn L Penney⁴⁸, Meir J Stampfer⁴⁹, Victoria L Stevens⁴⁴, Stephanie J Weinstein⁴¹, Antonia Trichopoulou⁵⁰, Bas H Bueno-de-Mesquita⁵¹, Anne Tjønneland⁵², David G Cox⁵³; BPC3 consortium; Lovise Maehle⁵⁴, Johanna Schleutker⁵⁵, Sara Lindström⁴⁶, Fredrik Wiklund²

Affiliations

¹ Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden. Academic Primary Healthcare Center, Stockholm County Council, Karolinska Institute, Stockholm, Sweden. robert.szulkin@ki.se.
² Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
³ The Institute of Cancer Research, London, United Kingdom. Royal Marsden National Health Service (NHS) Foundation Trust, London and Sutton, United Kingdom.
⁴ Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.
⁵ The Institute of Cancer Research, London, United Kingdom.
⁶ Institute of Population Health, University of Manchester, Manchester, United Kingdom. Warwick Medical School, University of Warwick, Coventry, United Kingdom.
⁷ Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia.
⁸ Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Grattan Street, Parkville, Victoria, Australia.
⁹ Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia.
¹⁰ Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California.
¹¹ Department of Medical Biochemistry and Genetics, Institute of Biomedicine Kiinamyllynkatu 10, University of Turku, Turku, Finland.
¹² Department of Urology, Tampere University Hospital and Medical School, University of Tampere, Tampere, Finland.
¹³ Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
¹⁴ Cancer Epidemiology, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
¹⁵ Department of Oncology, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom. Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Cambridge, United Kingdom.
¹⁶ School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
¹⁷ Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom; Faculty of Medical Science, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
¹⁸ Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.
¹⁹ Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom. University College London, Department of Applied Health Research, 1-19 Torrington Place, London, United Kingdom.
²⁰ Clinical Gerontology Unit, University of Cambridge, Cambridge, United Kingdom.
²¹ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington. Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington.
²² Mayo Clinic, Rochester, Minnesota.
²³ Department of Urology, University Hospital Ulm, Ulm, Germany.
²⁴ Institute of Human Genetics, University Hospital Ulm, Ulm, Germany.
²⁵ Department of Urology, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich, Germany.
²⁶ Division of Urologic Surgery, Brigham and Womens Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts.
²⁷ International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
²⁸ Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, Utah. George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah.
²⁹ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany. German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
³⁰ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
³¹ Saarland Cancer Registry, Saarbrücken, Germany.
³² Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida.
³³ Biostatistics Program, Moffitt Cancer Center, Tampa, Florida.
³⁴ Department of Urology and Alexandrovska University Hospital, Medical University, Sofia, Bulgaria.
³⁵ Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University, Sofia, Bulgaria.
³⁶ Molecular Cancer Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia.
³⁷ Department of Genetics, Portuguese Oncology Institute, Porto, Portugal. Biomedical Sciences Institute (ICBAS), University of Porto, Porto, Portugal.
³⁸ Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
³⁹ The University of Surrey, Guildford, Surrey, United Kingdom.
⁴⁰ Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Science, Queensland University of Technology, Brisbane, Australia.
⁴¹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
⁴² Washington University School of Medicine, St. Louis, Missouri.
⁴³ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland. Core Genotyping Facility, Frederick National Laboratory for Cancer Research, Gaithersburg, Maryland.
⁴⁴ Epidemiology Research Program, American Cancer Society, Atlanta, Georgia.
⁴⁵ Departments of Epidemiology and Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. Department of Medicine, Harvard Medical School, Boston, Massachusetts.
⁴⁶ Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
⁴⁷ Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii.
⁴⁸ Department of Medicine, Harvard Medical School, Boston, Massachusetts. Department of Epidemiology, Brigham and Women's Hospital Channing Laboratory, Boston, Massachusetts. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
⁴⁹ Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
⁵⁰ Hellenic Health Foundation, Athens, Greece. Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens Medical School, Athens, Greece. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece.
⁵¹ Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, the Netherlands. Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom. Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
⁵² Danish Cancer Society Research Center, Copenhagen, Denmark.
⁵³ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. Cancer Research Center of Lyon, INSERM UMR1052, Center Léon Bérard, Lyon, France.
⁵⁴ Inherited Cancer Research Group, Department for Medical Genetics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
⁵⁵ Department of Medical Biochemistry and Genetics, Institute of Biomedicine Kiinamyllynkatu 10, University of Turku, Turku, Finland. BioMediTech, University of Tampere and FimLab Laboratories, Tampere, Finland.

PMID: 26307654
PMCID: PMC5674990
DOI: 10.1158/1055-9965.EPI-15-0543

Genome-wide association study of prostate cancer-specific survival

Robert Szulkin et al. Cancer Epidemiol Biomarkers Prev. 2015 Nov.

. 2015 Nov;24(11):1796-800.

doi: 10.1158/1055-9965.EPI-15-0543. Epub 2015 Aug 25.

Authors

Affiliations

¹ Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden. Academic Primary Healthcare Center, Stockholm County Council, Karolinska Institute, Stockholm, Sweden. robert.szulkin@ki.se.
² Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
³ The Institute of Cancer Research, London, United Kingdom. Royal Marsden National Health Service (NHS) Foundation Trust, London and Sutton, United Kingdom.
⁴ Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.
⁵ The Institute of Cancer Research, London, United Kingdom.
⁶ Institute of Population Health, University of Manchester, Manchester, United Kingdom. Warwick Medical School, University of Warwick, Coventry, United Kingdom.
⁷ Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia.
⁸ Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Grattan Street, Parkville, Victoria, Australia.
⁹ Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia.
¹⁰ Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California.
¹¹ Department of Medical Biochemistry and Genetics, Institute of Biomedicine Kiinamyllynkatu 10, University of Turku, Turku, Finland.
¹² Department of Urology, Tampere University Hospital and Medical School, University of Tampere, Tampere, Finland.
¹³ Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
¹⁴ Cancer Epidemiology, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
¹⁵ Department of Oncology, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom. Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Cambridge, United Kingdom.
¹⁶ School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
¹⁷ Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom; Faculty of Medical Science, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
¹⁸ Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.
¹⁹ Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom. University College London, Department of Applied Health Research, 1-19 Torrington Place, London, United Kingdom.
²⁰ Clinical Gerontology Unit, University of Cambridge, Cambridge, United Kingdom.
²¹ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington. Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington.
²² Mayo Clinic, Rochester, Minnesota.
²³ Department of Urology, University Hospital Ulm, Ulm, Germany.
²⁴ Institute of Human Genetics, University Hospital Ulm, Ulm, Germany.
²⁵ Department of Urology, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich, Germany.
²⁶ Division of Urologic Surgery, Brigham and Womens Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts.
²⁷ International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
²⁸ Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, Utah. George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah.
²⁹ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany. German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
³⁰ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
³¹ Saarland Cancer Registry, Saarbrücken, Germany.
³² Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida.
³³ Biostatistics Program, Moffitt Cancer Center, Tampa, Florida.
³⁴ Department of Urology and Alexandrovska University Hospital, Medical University, Sofia, Bulgaria.
³⁵ Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University, Sofia, Bulgaria.
³⁶ Molecular Cancer Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia.
³⁷ Department of Genetics, Portuguese Oncology Institute, Porto, Portugal. Biomedical Sciences Institute (ICBAS), University of Porto, Porto, Portugal.
³⁸ Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
³⁹ The University of Surrey, Guildford, Surrey, United Kingdom.
⁴⁰ Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Science, Queensland University of Technology, Brisbane, Australia.
⁴¹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
⁴² Washington University School of Medicine, St. Louis, Missouri.
⁴³ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland. Core Genotyping Facility, Frederick National Laboratory for Cancer Research, Gaithersburg, Maryland.
⁴⁴ Epidemiology Research Program, American Cancer Society, Atlanta, Georgia.
⁴⁵ Departments of Epidemiology and Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. Department of Medicine, Harvard Medical School, Boston, Massachusetts.
⁴⁶ Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
⁴⁷ Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii.
⁴⁸ Department of Medicine, Harvard Medical School, Boston, Massachusetts. Department of Epidemiology, Brigham and Women's Hospital Channing Laboratory, Boston, Massachusetts. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
⁴⁹ Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
⁵⁰ Hellenic Health Foundation, Athens, Greece. Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens Medical School, Athens, Greece. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece.
⁵¹ Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, the Netherlands. Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom. Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
⁵² Danish Cancer Society Research Center, Copenhagen, Denmark.
⁵³ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. Cancer Research Center of Lyon, INSERM UMR1052, Center Léon Bérard, Lyon, France.
⁵⁴ Inherited Cancer Research Group, Department for Medical Genetics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
⁵⁵ Department of Medical Biochemistry and Genetics, Institute of Biomedicine Kiinamyllynkatu 10, University of Turku, Turku, Finland. BioMediTech, University of Tampere and FimLab Laboratories, Tampere, Finland.

PMID: 26307654
PMCID: PMC5674990
DOI: 10.1158/1055-9965.EPI-15-0543

Abstract

Background: Unnecessary intervention and overtreatment of indolent disease are common challenges in clinical management of prostate cancer. Improved tools to distinguish lethal from indolent disease are critical.

Methods: We performed a genome-wide survival analysis of cause-specific death in 24,023 prostate cancer patients (3,513 disease-specific deaths) from the PRACTICAL and BPC3 consortia. Top findings were assessed for replication in a Norwegian cohort (CONOR).

Results: We observed no significant association between genetic variants and prostate cancer survival.

Conclusions: Common genetic variants with large impact on prostate cancer survival were not observed in this study.

Impact: Future studies should be designed for identification of rare variants with large effect sizes or common variants with small effect sizes.

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Conflict of interest statement

Conflict of Interest: There is no conflict of interest.

References

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Genome-wide association study of prostate cancer-specific survival

Affiliations

Genome-wide association study of prostate cancer-specific survival

Authors

Affiliations

Abstract

Conflict of interest statement

References

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MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical