Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of three new genome-wide association studies (GWAS) and one prior scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of nine promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; (P=2.33x10^{-21})), rs2523607 at 6p21.33 (HLA-B; (2.40x10^{-10})), rs79480871 at 2p23.3 (NCOA1; (P=4.23x10^{-8})), and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; (P=9.98x10^{-13}) and (P=3.63x10^{-11}), respectively). These data provide substantial new evidence for genetic susceptibility to this B-cell malignancy, and point towards pathways involved in immune recognition and immune function in the pathogenesis of DLBCL.