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Germline variation at 8q24 and prostate cancer risk in men of European ancestry.
Matejcic, Marco; Saunders, Edward J; Dadaev, Tokhir; Brook, Mark N; Wang, Kan; Sheng, Xin; Olama, Ali Amin Al; Schumacher, Fredrick R; Ingles, Sue A; Govindasami, Koveela; Benlloch, Sara; Berndt, Sonja I; Albanes, Demetrius; Koutros, Stella; Muir, Kenneth; Stevens, Victoria L; Gapstur, Susan M; Tangen, Catherine M; Batra, Jyotsna; Clements, Judith; Gronberg, Henrik; Pashayan, Nora; Schleutker, Johanna; Wolk, Alicja; West, Catharine; Mucci, Lorelei; Kraft, Peter; Cancel-Tassin, Géraldine; Sorensen, Karina D; Maehle, Lovise; Grindedal, Eli M; Strom, Sara S; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Travis, Ruth C; Hamilton, Robert J; Rosenstein, Barry; Lu, Yong-Jie; Giles, Graham G; Kibel, Adam S; Vega, Ana; Bensen, Jeanette T; Kogevinas, Manolis; Penney, Kathryn L; Park, Jong Y; Stanford, Janet L; Cybulski, Cezary; Nordestgaard, Børge G; Brenner, Hermann.
Afiliação
  • Matejcic M; Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, 90033, USA.
  • Saunders EJ; The Institute of Cancer Research, London, SW7 3RP, UK.
  • Dadaev T; The Institute of Cancer Research, London, SW7 3RP, UK.
  • Brook MN; The Institute of Cancer Research, London, SW7 3RP, UK.
  • Wang K; Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, 90033, USA.
  • Sheng X; Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, 90033, USA.
  • Olama AAA; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge, CB1 8RN, UK.
  • Schumacher FR; Department of Clinical Neurosciences, University of Cambridge, Cambridge, CB2 0QQ, UK.
  • Ingles SA; Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, 44106-7219, USA.
  • Govindasami K; Seidman Cancer Center, University Hospitals, Cleveland, OH, 44106, USA.
  • Benlloch S; Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, 90033, USA.
  • Berndt SI; The Institute of Cancer Research, London, SW7 3RP, UK.
  • Albanes D; The Institute of Cancer Research, London, SW7 3RP, UK.
  • Koutros S; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge, CB1 8RN, UK.
  • Muir K; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, 20892, USA.
  • Stevens VL; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, 20892, USA.
  • Gapstur SM; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, 20892, USA.
  • Tangen CM; Institute of Population Health, University of Manchester, Manchester, M13 9PL, UK.
  • Batra J; Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK.
  • Clements J; Epidemiology Research Program, American Cancer Society, 250 Williams Street, Atlanta, GA, 30303, USA.
  • Gronberg H; Epidemiology Research Program, American Cancer Society, 250 Williams Street, Atlanta, GA, 30303, USA.
  • Pashayan N; SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
  • Schleutker J; Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Science, Queensland University of Technology, Brisbane, QLD, 4059, Australia.
  • Wolk A; Translational Research Institute, Brisbane, QLD, 4102, Australia.
  • West C; Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Science, Queensland University of Technology, Brisbane, QLD, 4059, Australia.
  • Mucci L; Translational Research Institute, Brisbane, QLD, 4102, Australia.
  • Kraft P; Department of Medical Epidemiology and Biostatistics, Karolinska Institute, SE-171 77, Stockholm, Sweden.
  • Cancel-Tassin G; Centre for Cancer Genetic Epidemiology, Department of Oncology, Strangeways Research Laboratory, University of Cambridge, Cambridge, CB1 8RN, UK.
  • Sorensen KD; Department of Applied Health Research, University College London, London, WC1E 7HB, UK.
  • Maehle L; Department of Medical Biochemistry and Genetics, Institute of Biomedicine, University of Turku, FI-20014, Turku, Finland.
  • Grindedal EM; Tyks Microbiology and Genetics, Department of Medical Genetics, Turku University Hospital, 20521, Turku, Finland.
  • Strom SS; BioMediTech, University of Tampere, 33520, Tampere, Finland.
  • Neal DE; Division of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, SE-171 77, Stockholm, Sweden.
  • Hamdy FC; Division of Cancer Sciences, Manchester Academic Health Science Centre, Radiotherapy Related Research, Manchester NIHR Biomedical Research Centre, The Christie Hospital NHS Foundation Trust, University of Manchester, Manchester, M13 9PL, UK.
  • Donovan JL; Department of Epidemiology, Harvard School of Public Health, Boston, MA, 02115, USA.
  • Travis RC; Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.
  • Hamilton RJ; GRC N°5 ONCOTYPE-URO, UPMC Univ Paris 06, Tenon Hospital, F-75020, Paris, France.
  • Rosenstein B; CeRePP, Tenon Hospital, F-75020, Paris, France.
  • Lu YJ; Department of Molecular Medicine, Aarhus University Hospital, 8200, Aarhus N, Denmark.
  • Giles GG; Department of Clinical Medicine, Aarhus University, 8200, Aarhus N, Denmark.
  • Kibel AS; Department of Medical Genetics, Oslo University Hospital, 0424, Oslo, Norway.
  • Vega A; Department of Medical Genetics, Oslo University Hospital, 0424, Oslo, Norway.
  • Bensen JT; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
  • Kogevinas M; Department of Oncology, Addenbrooke's Hospital, University of Cambridge, Cambridge, CB2 0QQ, UK.
  • Penney KL; Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Cambridge, CB2 0RE, UK.
  • Park JY; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, OX1 2JD, UK.
  • Stanford JL; School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol, BS8 2PS, UK.
  • Cybulski C; Cancer Epidemiology, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK.
  • Nordestgaard BG; Department of Surgical Oncology, Princess Margaret Cancer Centre, Toronto, ON, M5G 2M9, Canada.
  • Brenner H; Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Nat Commun ; 9(1): 4616, 2018 11 05.
Article em En | MEDLINE | ID: mdl-30397198
ABSTRACT
Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10-15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62-4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Cromossomos Humanos Par 8 / Predisposição Genética para Doença / População Branca Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans / Male Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Cromossomos Humanos Par 8 / Predisposição Genética para Doença / População Branca Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans / Male Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos