Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility.

Autor: Sud A; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK., Thomsen H; Division of Molecular Genetic Epidemiology, German Cancer Research Centre, Heidelberg, 69120, Germany., Law PJ; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK., Försti A; Division of Molecular Genetic Epidemiology, German Cancer Research Centre, Heidelberg, 69120, Germany.; Centre for Primary Health Care Research, Lund University, Malmö, 221 00, Sweden., Filho MIDS; Division of Molecular Genetic Epidemiology, German Cancer Research Centre, Heidelberg, 69120, Germany., Holroyd A; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK., Broderick P; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK., Orlando G; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK., Lenive O; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK., Wright L; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK., Cooke R; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK., Easton D; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK.; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK., Pharoah P; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK.; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK., Dunning A; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK., Peto J; Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK., Canzian F; Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, 69120, Germany., Eeles R; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.; Royal Marsden NHS Foundation Trust, London, SM2 5NG, UK., Kote-Jarai Z; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK., Muir K; Institute of Population Health, University of Manchester, Manchester, M1 3BB, UK.; Division of Health Sciences, Warwick Medical School, Warwick University, Warwick, CV4 7AL, UK., Pashayan N; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.; Department of Applied Health Research, University College London, London, WC1E 7HB, UK., Hoffmann P; Department of Biomedicine, Division of Medical Genetics, University of Basel, Basel, 4031, Switzerland.; Institute of Human Genetics, University of Bonn, Bonn, 53127, Germany., Nöthen MM; Institute of Human Genetics, University of Bonn, Bonn, 53127, Germany.; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, 53127, Germany., Jöckel KH; University of Duisburg-Essen, Essen, 47057, Germany., Strandmann EPV; Department of Internal Medicine, University Hospital of Cologne, Cologne, 50937, Germany., Lightfoot T; Department of Health Sciences, University of York, York, YO10 5DD, UK., Kane E; Department of Health Sciences, University of York, York, YO10 5DD, UK., Roman E; Department of Health Sciences, University of York, York, YO10 5DD, UK., Lake A; MRC University of Glasgow Centre for Virus Research, Glasgow, G61 1QH, UK., Montgomery D; MRC University of Glasgow Centre for Virus Research, Glasgow, G61 1QH, UK., Jarrett RF; MRC University of Glasgow Centre for Virus Research, Glasgow, G61 1QH, UK., Swerdlow AJ; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.; Division of Breast Cancer Research, The Institute of Cancer Research, London, SW7 3RP, UK., Engert A; Department of Internal Medicine, University Hospital of Cologne, Cologne, 50937, Germany., Orr N; Division of Molecular Pathology, The Institute of Cancer Research, London, SW7 3RP, UK., Hemminki K; Division of Molecular Genetic Epidemiology, German Cancer Research Centre, Heidelberg, 69120, Germany.; Centre for Primary Health Care Research, Lund University, Malmö, 221 00, Sweden., Houlston RS; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK. richard.houlston@icr.ac.uk.; Division of Molecular Pathology, The Institute of Cancer Research, London, SW7 3RP, UK. richard.houlston@icr.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2017 Dec 01; Vol. 8 (1), pp. 1892. Date of Electronic Publication: 2017 Dec 01.
DOI: 10.1038/s41467-017-00320-1
Abstrakt: Several susceptibility loci for classical Hodgkin lymphoma have been reported. However, much of the heritable risk is unknown. Here, we perform a meta-analysis of two existing genome-wide association studies, a new genome-wide association study, and replication totalling 5,314 cases and 16,749 controls. We identify risk loci for all classical Hodgkin lymphoma at 6q22.33 (rs9482849, P = 1.52 × 10 -8 ) and for nodular sclerosis Hodgkin lymphoma at 3q28 (rs4459895, P = 9.43 × 10 -17 ), 6q23.3 (rs6928977, P = 4.62 × 10 -11 ), 10p14 (rs3781093, P = 9.49 × 10 -13 ), 13q34 (rs112998813, P = 4.58 × 10 -8 ) and 16p13.13 (rs34972832, P = 2.12 × 10 -8 ). Additionally, independent loci within the HLA region are observed for nodular sclerosis Hodgkin lymphoma (rs9269081, HLA-DPB1*03:01, Val86 in HLA-DRB1) and mixed cellularity Hodgkin lymphoma (rs1633096, rs13196329, Val86 in HLA-DRB1). The new and established risk loci localise to areas of active chromatin and show an over-representation of transcription factor binding for determinants of B-cell development and immune response.
Databáze: MEDLINE