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

Cerhan, J. R.; Berndt, S. I.; Vijai, J.; Ghesquières, H.; Mckay, J.; Wang, S. S.; Wang, Z.; Yeager, M.; Conde, L.; De Bakker, P. I. W.; Nieters, A.; Cox, D.; Burdett, L.; Monnereau, A.; Flowers, C. R.; De Roos, A. J.; Brooks-Wilson, A. R.; Lan, Q.; Severi, G.; Melbye, M.; Gu, J.; Jackson, R. D.; Kane, E.; Teras, L. R.; Purdue, M. P.; Vajdic, C. M.; Spinelli, J. J.; Giles, G. G.; Albanes, D.; Kelly, R. S.; Zucca, M.; Bertrand, K. A.; Zeleniuch-Jacquotte, A.; Lawrence, C.; Hutchinson, A.; Zhi, D.; Habermann, T. M.; Link, B. K.; Novak, A. J.; Dogan, A.; Asmann, Y. W.; Liebow, M.; Thompson, C. A.; Ansell, S. M.; Witzig, T. E.; Weiner, G. J.; Veron, A. S.; Zelenika, D.; Tilly, H.; Haioun, C.; Molina, T. J.; Hjalgrim, H.; Glimelius, B.; Adami, H. -O.; Bracci, P. M.; Riby, J.; Smith, M. T.; Holly, E. A.; Cozen, W.; Hartge, P.; Morton, L. M.; Severson, R. K.; Tinker, L. F.; North, K. E.; Becker, N.; Benavente, Y.; Boffetta, P.; Brennan, P.; Foretova, L.; Maynadie, M.; Staines, A.; Lightfoot, T.; Crouch, S.; Smith, A.; Roman, E.; Diver, W. R.; Offit, K.; Zelenetz, A.; Klein, R. J.; Villano, D. J.; Zheng, T.; Zhang, Y.; Holford, T. R.; Kricker, A.; Turner, J.; Southey, M. C.; Clavel, J.; Virtamo, J.; Weinstein, S.; Riboli, E.; Vineis, P.; Kaaks, R.; Trichopoulos, D.; Vermeulen, R. C. H.; Boeing, H.; Tjonneland, A.; Angelucci, E.; Di Lollo, S.; Rais, M.; Birmann, B. M.; Laden, F.; Giovannucci, E.; Kraft, P.; Huang, J.; Ma, B.; Ye, Y.; Chiu, B. C. H.; Sampson, J.; Liang, L.; Park, J. -H.; Chung, C. C.; Weisenburger, D. D.; Chatterjee, N.; Fraumeni, J. F.; Slager, S. L.; Wu, X.; De Sanjose, S.; Smedby, K. E.; Salles, G.; Skibola, C. F.; Rothman, N.; Chanock, S. J.

doi:10.1038/ng.3105

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. © 2014 Nature America, Inc. All rights reserved.

Cerhan, J., Berndt, S., Vijai, J., Ghesquières, H., McKay, J., Wang, S., et al. (2014). Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma. NATURE GENETICS, 46(11), 1233-1238 [10.1038/ng.3105].