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

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

Published Web Location

https://doi.org/10.1038/ng.3105
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.

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