Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma.

Bernatsky S, Velásquez García HA, Spinelli JJ, Gaffney P, Smedby KE, Ramsey-Goldman R, Wang SS, Adami HO, Albanes D, Angelucci E, Ansell SM, Asmann YW, Becker N, Benavente Y, Berndt SI, Bertrand KA, Birmann BM, Boeing H, Boffetta P, Bracci PM, Brennan P, Brooks-Wilson AR, Cerhan JR, Chanock SJ, Clavel J, Conde L, Cotenbader KH, Cox DG, Cozen W, Crouch S, De Roos AJ, de Sanjose S, Di Lollo S, Diver WR, Dogan A, Foretova L, Ghesquières H, Giles GG, Glimelius B, Habermann TM, Haioun C, Hartge P, Hjalgrim H, Holford TR, Holly EA, Jackson RD, Kaaks R, Kane E, Kelly RS, Klein RJ, Kraft P, Kricker A, Lan Q, Lawrence C, Liebow M, Lightfoot T, Link BK, Maynadie M, McKay J, Melbye M, Molina TJ, Monnereau A, Morton LM, Nieters A, North KE, Novak AJ, Offit K, Purdue MP, Rais M, Riby J, Roman E, Rothman N, Salles G, Severi G, Severson RK, Skibola CF, Slager SL, Smith A, Smith MT, Southey MC, Staines A, Teras LR, Thompson CA, Tilly H, Tinker LF, Tjonneland A, Turner J, Vajdic CM, Vermeulen RCH, Vijai J, Vineis P, Virtamo J, Wang Z, Weinstein S, Witzig TE, Zelenetz A, Zeleniuch-Jacquotte A, Zhang Y, Zheng T, Zucca M, Clarke AE
Lupus Sci Med 4 e000187 01/01/2017


Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL.

Methods: GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis.

Results: Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765.

Conclusions: These data suggest several plausible genetic links between DLBCL and SLE.

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