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

in Lupus science & medicine by Sasha Bernatsky, Héctor A Velásquez García, John J Spinelli, Patrick Gaffney, Karin E Smedby, Rosalind Ramsey-Goldman, Sophia S Wang, Hans-Olov Adami, Demetrius Albanes, Emanuele Angelucci, Stephen M Ansell, Yan W Asmann, Nikolaus Becker, Yolanda Benavente, Sonja I Berndt, Kimberly A Bertrand, Brenda M Birmann, Heiner Boeing, Paolo Boffetta, Paige M Bracci, Paul Brennan, Angela R Brooks-Wilson, James R Cerhan, Stephen J Chanock, Jacqueline Clavel, Lucia Conde, Karen H Cotenbader, David G Cox, Wendy Cozen, Simon Crouch, Anneclaire J De Roos, Silvia de Sanjose, Simonetta Di Lollo, W Ryan Diver, Ahmet Dogan, Lenka Foretova, Hervé Ghesquières, Graham G Giles, Bengt Glimelius, Thomas M Habermann, Corinne Haioun, Patricia Hartge, Henrik Hjalgrim, Theodore R Holford, Elizabeth A Holly, Rebecca D Jackson, Rudolph Kaaks, Eleanor Kane, Rachel S Kelly, Robert J Klein, Peter Kraft, Anne Kricker, Qing Lan, Charles Lawrence, Mark Liebow, Tracy Lightfoot, Brian K Link, Marc Maynadie, James McKay, Mads Melbye, Thierry J Molina, Alain Monnereau, Lindsay M Morton, Alexandra Nieters, Kari E North, Anne J Novak, Kenneth Offit, Mark P Purdue, Marco Rais, Jacques Riby, Eve Roman, Nathaniel Rothman, Gilles Salles, Gianluca Severi, Richard K Severson, Christine F Skibola, Susan L Slager, Alex Smith, Martyn T Smith, Melissa C Southey, Anthony Staines, Lauren R Teras, Carrie A Thompson, Hervé Tilly, Lesley F Tinker, Anne Tjonneland, Jenny Turner, Claire M Vajdic, Roel C H Vermeulen, Joseph Vijai, Paolo Vineis, Jarmo Virtamo, Zhaoming Wang, Stephanie Weinstein, Thomas E Witzig, Andrew Zelenetz, Anne Zeleniuch-Jacquotte, Yawei Zhang, Tongzhang Zheng, Mariagrazia Zucca, Ann E Clarke

TLDR

  • The study identifies several lupus-related SNPs associated with increased risk of diffuse large B-cell lymphoma (DLBCL) in European Caucasians.
  • The findings suggest plausible genetic links between DLBCL and SLE and may have implications for developing new biomarkers or therapeutic targets.

Abstract

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

Overview

  • The study aimed to investigate the determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in systemic lupus erythematosus (SLE).
  • The study used data from a recent lymphoma genome-wide association study (GWAS) and pooled data from 3857 DLBCL cases and 7666 general-population controls.
  • The primary objective was to assess whether certain lupus-related single nucleotide polymorphisms (SNPs) are associated with DLBCL risk.

Comparative Analysis & Findings

  • Two SNPs, rs4810485 (CD40) and rs1270942 (HLA), were convincingly associated with DLBCL risk, with ORs per risk allele of 1.09 and 1.17, respectively.
  • Additional SNPs, rs2205960 (related to TNFSF4) and rs12537284 (chromosome 7q32, IRF5 gene), showed associations with DLBCL risk, but with p-values of 0.0549 and 0.0765, respectively.
  • The study suggests several plausible genetic links between DLBCL and SLE, but further research is needed to confirm these findings.

Implications and Future Directions

  • The study's findings may have implications for the development of new biomarkers or therapeutic targets for DLBCL in patients with SLE.
  • Future studies could investigate the functional relevance of these associated SNPs and explore their role in the development of DLBCL.
  • The identification of specific genetic variants may also inform individualized risk prediction and population-based screening strategies for DLBCL.
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