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

By 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 Melbye, Jian 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, Alex 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 and Stephen J. Chanock


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

Year: 2014
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