Sud, Amit ORCID: 0000-0002-6133-0164, Thomsen, Hauke ORCID: 0000-0001-5951-3116, Orlando, Giulia, Foersti, Asta, Law, Philip J., Broderick, Peter ORCID: 0000-0002-8348-5829, Cooke, Rosie, Hariri, Fadi, Pastinen, Tomi, Easton, Douglas F., Pharoah, Paul D. P., Dunning, Alison M., Peto, Julian, Canzian, Federico ORCID: 0000-0002-4261-4583, Eeles, Rosalind ORCID: 0000-0002-3698-6241, Kote-Jarai, ZSofia, Muir, Kenneth, Pashayan, Nora, Campa, Daniele, Hoffmann, Per, Noethen, Markus M., Joeckel, Karl-Heinz, von Strandmann, Elke Pogge, Swerdlow, Anthony J., Engert, Andreas, Orr, Nick, Hemminki, Kari and Houlston, Richard S. (2018). Genome-wide association study implicates immune dysfunction in the development of Hodgkin lymphoma. Blood, 132 (19). S. 2040 - 2053. WASHINGTON: AMER SOC HEMATOLOGY. ISSN 1528-0020

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Abstract

To further our understanding of inherited susceptibility to Hodgkin lymphoma (HL), we performed a meta-analysis of 7 genome-wide association studies totaling 5325 HL cases and 22 423 control patients. We identify 5 new HL risk loci at 6p21.31 (rs649775; P = 2.11 x 10(9), 6q23.3 (rs1002658; P = 2.97 x 10(-8)), 11q23.1 (rs7111520; P = 1.44 x 10(-11)), 16p11.2 (rs6565176; P = 4.00 x 10(-8)), and 20q13.12 (rs2425752; P = 2.01 x 10(-8)). Integration of gene expression, histone modification, and in situ promoter capture Hi-C data at the 5 new and 13 known risk loci implicates dysfunction of the germinal center reaction, disrupted T-cell differentiation and function, and constitutive NF-kappa B activation as mechanisms of predisposition. These data provide further insights into the genetic susceptibility and biology of HL.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Sud, AmitUNSPECIFIEDorcid.org/0000-0002-6133-0164UNSPECIFIED
Thomsen, HaukeUNSPECIFIEDorcid.org/0000-0001-5951-3116UNSPECIFIED
Orlando, GiuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Foersti, AstaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Law, Philip J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Broderick, PeterUNSPECIFIEDorcid.org/0000-0002-8348-5829UNSPECIFIED
Cooke, RosieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hariri, FadiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pastinen, TomiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Easton, Douglas F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pharoah, Paul D. P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dunning, Alison M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peto, JulianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Canzian, FedericoUNSPECIFIEDorcid.org/0000-0002-4261-4583UNSPECIFIED
Eeles, RosalindUNSPECIFIEDorcid.org/0000-0002-3698-6241UNSPECIFIED
Kote-Jarai, ZSofiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muir, KennethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pashayan, NoraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Campa, DanieleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoffmann, PerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Noethen, Markus M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Joeckel, Karl-HeinzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Strandmann, Elke PoggeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Swerdlow, Anthony J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Engert, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Orr, NickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hemminki, KariUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Houlston, Richard S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-165891
DOI: 10.1182/blood-2018-06-855296
Journal or Publication Title: Blood
Volume: 132
Number: 19
Page Range: S. 2040 - 2053
Date: 2018
Publisher: AMER SOC HEMATOLOGY
Place of Publication: WASHINGTON
ISSN: 1528-0020
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
REED-STERNBERG CELLS; CENTER B-CELL; TRANSCRIPTION FACTOR; TARGET GENE; C-MYC; EXPRESSION; RECEPTOR; DISEASE; PROTEIN; RISKMultiple languages
HematologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/16589

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