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

Thorball, Christian W; Oudot-Mellakh, Tiphaine; Ehsan, Nava; Hammer, Christian; Santoni, Federico A; Niay, Jonathan; Costagliola, Dominique; Goujard, Cécile; Meyer, Laurence; Wang, Sophia S; Hussain, Shehnaz K; Theodorou, Ioannis; Cavassini, Matthias; Rauch, Andri; Battegay, Manuel; Hoffmann, Matthias; Schmid, Patrick; Bernasconi, Enos; Günthard, Huldrych F; Mohammadi, Pejman; ... (2021). Genetic variation near CXCL12 is associated with susceptibility to HIV-related non-Hodgkin lymphoma. Haematologica - the hematology journal, 106(8), pp. 2233-2241. Ferrata-Storti Foundation 10.3324/haematol.2020.247023

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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.

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