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Genome-wide association study implicates immune dysfunction in the development of Hodgkin lymphoma.


Type

Article

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Authors

Sud, Amit 
Thomsen, Hauke 
Orlando, Giulia 
Försti, Asta 
Law, Philip J 

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.

Description

Keywords

Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Germinal Center, Histone Code, Hodgkin Disease, Humans, Immunity, NF-kappa B, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, T-Lymphocytes

Journal Title

Blood

Conference Name

Journal ISSN

0006-4971
1528-0020

Volume Title

Publisher

American Society of Hematology
Sponsorship
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)
Includes Bloodwise, Wellcome Trust and CRUK