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

Blood. 2018 Nov 8;132(19):2040-2052. doi: 10.1182/blood-2018-06-855296. Epub 2018 Sep 7.

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 × 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 5 new and 13 known risk loci implicates dysfunction of the germinal center 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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • NF-kappa B