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

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Publication date

2014-01-01

Authors

Cerhan, James R.
Berndt, Sonja I.
Vijai, Joseph
Ghesquières, Hervé
McKay, James
Wang, Sophia S.
Wang, Zhaoming
Yeager, Meredith
Conde, Lucia
De Bakker, Paul I W

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DOI

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

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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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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 2014, 'Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma', Nature Genetics, vol. 46, no. 11, pp. 1233-1238. https://doi.org/10.1038/ng.3105

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https://dspace.library.uu.nl/handle/1874/305083