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

• Authors: James R. Cerhan, Mayo Clinic; Sonja I. Berndt, National Cancer Institute; Joseph Vijai, National Cancer Institute; Herve Ghesquieres, Centre Léon Bérard; James McKay, International Agency for Research on Cancer; Sophia S. Wang, City of Hope Beckman Research Institute; Zhaoming Wang, National Cancer Institute; Meredith Yeager, National Cancer Institute; Lucia Conde, University of Alabama; Paul I. W. de Bakker, University Medical Center Utrecht; Alexandra Nieters, University Medical Center Freiburg; David Cox, Centre Léon Bérard; Laurie Burdett, National Cancer Institute; Alain Monnereau, Centre for Research in Epidemiology and Population Health; Christopher Flowers, Emory University; Anneclaire J. De Roos, National Cancer Institute; Angela R. Brooks-Wilson, Simon Fraser University; Qing Lan, National Cancer Institute; Gianluca Severi, Human Genetics Foundation; Mads Melbye, Statens Serum Institut; Jian Gu, University of Texas; Rebecca D. Jackson, Ohio State University; Eleanor Kane, University of York; Lauren R. Teras, American Cancer Society; Mark P. Purdue, National Cancer Institute; Claire M. Vajdic, University of New South Wales; John J. Spinelli, University of British Columbia; Graham G. Giles, University of Melbourne; Demetrius Albanes, National Cancer Institute; Christine Skibola, Emory University
• Journal Title: Nature Genetics
• Volume: Volume 46, Number 11
• Publisher: Nature Research (part of Springer Nature) | 2014-11-01, Pages 1233-1238
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1038/ng.3105
• Subjects: Health Sciences, Oncology; Biology, Genetics
• Keywords: Science & Technology; Life Sciences & Biomedicine; Genetics & Heredity; NON-HODGKIN-LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; NECROSIS-FACTOR TNF; FOLLICULAR LYMPHOMA; COMMON VARIANTS; RAL GTPASES; RISK; CANCER; TUMORIGENESIS; POPULATION

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 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 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 = 2.33 × 10 '21), rs2523607 at 6p21.33 (HLA-B; P = 2.40 × 10 '10), rs79480871 at 2p23.3 (NCOA1; P = 4.23 × 10 '8) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 × 10 '13 and 3.63 × 10 '11, respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL.