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 –10 ), 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-B activation as mechanisms of predisposition. These data provide further insights into the genetic susceptibility and biology of HL.
Immunobiology and Immunotherapy, Lymphoid Neoplasia