Blood 2018 Nov 7;132(19):2040-2052. Epub 2018 Sep 7.
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom.
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; = 2.11 × 10), 6q23.3 (rs1002658; = 2.97 × 10), 11q23.1 (rs7111520; = 1.44 × 10), 16p11.2 (rs6565176; = 4.00 × 10), and 20q13.12 (rs2425752; = 2.01 × 10). 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.
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