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

James R Cerhan, Sonja I Berndt, Joseph Vijai, Hervé Ghesquières, James McKay, Sophia S Wang, Zhaoming Wang, Meredith Yeager, Lucia Conde, Paul I W de Bakker, Alexandra Nieters, David Cox, Laurie Burdett, Alain Monnereau, Christopher R Flowers, Anneclaire J De Roos, Angela R Brooks-Wilson, Qing Lan, Gianluca Severi, Mads MelbyeJian Gu, Rebecca D Jackson, Eleanor Kane, Lauren R Teras, Mark P Purdue, Claire M Vajdic, John J Spinelli, Graham G Giles, Demetrius Albanes, Rachel S Kelly, Mariagrazia Zucca, Kimberly A Bertrand, Anne Zeleniuch-Jacquotte, Charles Lawrence, Amy Hutchinson, Degui Zhi, Thomas M Habermann, Brian K Link, Anne J Novak, Ahmet Dogan, Yan W Asmann, Mark Liebow, Carrie A Thompson, Stephen M Ansell, Thomas E Witzig, George J Weiner, Amelie S Veron, Diana Zelenika, Hervé Tilly, Corinne Haioun, Thierry Jo Molina, Henrik Hjalgrim, Bengt Glimelius, Hans-Olov Adami, Paige M Bracci, Jacques Riby, Martyn T Smith, Elizabeth A Holly, Wendy Cozen, Patricia Hartge, Lindsay M Morton, Richard K Severson, Lesley F Tinker, Kari E North, Nikolaus Becker, Yolanda Benavente, Paolo Boffetta, Paul Brennan, Lenka Foretova, Marc Maynadie, Anthony Staines, Tracy Lightfoot, Simon Crouch, Alexandra Gwen Smith, Eve Roman, W Ryan Diver, Kenneth Offit, Andrew Zelenetz, Robert J Klein, Danylo J Villano, Tongzhang Zheng, Yawei Zhang, Theodore R Holford, Anne Kricker, Jenny Turner, Melissa C Southey, Jacqueline Clavel, Jarmo Virtamo, Stephanie Weinstein, Elio Riboli, Paolo Vineis, Rudolph Kaaks, Dimitrios Trichopoulos, Roel C H Vermeulen, Heiner Boeing, Anne Tjonneland, Emanuele Angelucci, Simonetta Di Lollo, Marco Rais, Brenda M Birmann, Francine Laden, Edward Giovannucci, Peter Kraft, Jinyan Huang, Baoshan Ma, Yuanqing Ye, Brian C H Chiu, Joshua Sampson, Liming Liang, Ju-Hyun Park, Charles C Chung, Dennis D Weisenburger, Nilanjan Chatterjee, Joseph F Fraumeni, Susan L Slager, Xifeng Wu, Silvia de Sanjose, Karin E Smedby, Gilles Salles, Christine F Skibola, Nathaniel Rothman, Stephen J Chanock

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1233-1238
Number of pages6
JournalNature genetics
Issue number11
Early online date28 Sep 2014
Publication statusPublished - Nov 2014

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