Genome-wide association study implicates immune dysfunction in the development of Hodgkin lymphoma.
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Authors
Sud, Amit
Thomsen, Hauke
Orlando, Giulia
Försti, Asta
Law, Philip J
Broderick, Peter
Cooke, Rosie
Hariri, Fadi
Pastinen, Tomi
Easton, Douglas F
Pharoah, Paul DP
Dunning, Alison M
Peto, Julian
Canzian, Federico
Eeles, Rosalind
Kote-Jarai, ZSofia
Muir, Kenneth
Pashayan, Nora
Campa, Daniele
Hoffmann, Per
Nöthen, Markus M
Jöckel, Karl-Heinz
von Strandmann, Elke Pogge
Swerdlow, Anthony J
Engert, Andreas
Orr, Nick
Hemminki, Kari
Houlston, Richard S
Publication Date
2018-11-08Journal Title
Blood
ISSN
0006-4971
Publisher
American Society of Hematology
Language
English
Type
Article
This Version
NA
Metadata
Show full item recordCitation
Sud, A., Thomsen, H., Orlando, G., Försti, A., Law, P. J., Broderick, P., Cooke, R., et al. (2018). Genome-wide association study implicates immune dysfunction in the development of Hodgkin lymphoma.. Blood https://doi.org/10.1182/blood-2018-06-855296
Abstract
To further our understanding of inherited susceptibility to Hodgkin lymphoma (HL), we performed a meta-analysis of seven genome-wide association studies totalling 5,325 HL cases and 22,423 controls. We identify five new HL risk loci at 6p21.31 (rs649775, P = 2.11 × 10-10), 6q23.3 (rs1002658, P = 2.97 × 10-8), 11q23.1 (rs7111520, P = 1.44 × 10-11), 16p11.2 (rs6565176, P = 4.00 × 10-8) and 20q13.12 (rs2425752, P = 2.01 × 10-8). Integration of gene expression, histone modification and in situ promoter capture Hi-C data at the five new and 13 known risk loci implicates dysfunction of the germinal centre reaction, disrupted T-cell differentiation and function, and constitutive NF-κB activation as mechanisms of predisposition. These data provide further insights into the genetic susceptibility and biology of HL.
Sponsorship
Includes Bloodwise, Wellcome Trust and CRUK
Funder references
National Cancer Institute (U19CA148537)
Medical Research Council (G1000143)
Cancer Research UK (A16563)
European Commission (282510)
European Commission (223175)
Cancer Research UK (A10118)
Medical Research Council (G0401527)
Medical Research Council (MR/N003284/1)
Identifiers
External DOI: https://doi.org/10.1182/blood-2018-06-855296
This record's URL: https://www.repository.cam.ac.uk/handle/1810/285624
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http://www.rioxx.net/licenses/all-rights-reserved
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