Haematologica (Jul 2020)

Genetic variation near CXCL12 is associated with susceptibility to HIV-related non-Hodgkin lymphoma

  • Christian W. Thorball,
  • Tiphaine Oudot-Mellakh,
  • Nava Ehsan,
  • Christian Hammer,
  • Federico A. Santoni,
  • Jonathan Niay,
  • Dominique Costagliola,
  • Cécile Goujard,
  • Laurence Meyer,
  • Sophia S. Wang,
  • Shehnaz K. Hussain,
  • Ioannis Theodorou,
  • Matthias Cavassini,
  • Andri Rauch,
  • Manuel Battegay,
  • Matthias Hoffmann,
  • Patrick Schmid,
  • Enos Bernasconi,
  • Huldrych F. Günthard,
  • Pejman Mohammadi,
  • Paul J. McLaren,
  • Charles S. Rabkin,
  • Caroline Besson,
  • Jacques Fellay

DOI
https://doi.org/10.3324/haematol.2020.247023
Journal volume & issue
Vol. 106, no. 8

Abstract

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Human immunodeficiency virus (HIV) infection is associated with an increased risk of non-Hodgkin lymphoma (NHL). Even in the era of suppressive antiretroviral treatment, HIV-infected individuals remain at higher risk of developing NHL compared to the general population. To identify potential genetic risk loci, we performed case-control genome-wide association studies and a meta-analysis across three cohorts of HIV+ patients of European ancestry, including a total of 278 cases and 1924 matched controls. We observed a significant association with NHL susceptibility in the C-X-C motif chemokine ligand 12 (CXCL12) region on chromosome 10. A fine mapping analysis identified rs7919208 as the most likely causal variant (P = 4.77e-11), with the G>A polymorphism creating a new transcription factor binding site for BATF and JUND. These results suggest a modulatory role of CXCL12 regulation in the increased susceptibility to NHL observed in the HIV-infected population.