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Non-Hodgkin Lymphoma
Genetic variation near CXCL12 is associated with susceptibility to HIV-related non-Hodgkin lymphoma
Ferrata Storti Foundation
Haematologica 2021 Volume 106(8):2233-2241
Christian W. Thorball,1,2 Tiphaine Oudot-Mellakh,3 Nava Ehsan,4,5 Christian Hammer,6,7 Federico A. Santoni,8 Jonathan Niay,3 Dominique Costagliola,9 Cécile Goujard,10,11 Laurence Meyer,12 Sophia S. Wang,13 Shehnaz K. Hussain,14 Ioannis Theodorou,3 Matthias Cavassini,15 Andri Rauch,16 Manuel Battegay,17 Matthias Hoffmann,18 Patrick Schmid,19 Enos Bernasconi,20 Huldrych F. Günthard,21,22 Pejman Mohammadi,4,5 Paul J. McLaren,23,24 Charles S. Rabkin,25 Caroline Besson25-27 and Jacques Fellay1,2,28
1School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; 2Swiss Institute of Bioinformatics, Lausanne, Switzerland; 3Centre de Génétique Moléculaire et Chromosomique, GH La Pitié Salpêtrière, Paris, France; 4The Scripps Research Translational Institute, La Jolla, CA, USA; 5Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA; 6Department of Cancer Immunology, Genentech, South San Francisco, CA, USA; 7Department of Human Genetics, Genentech, South San Francisco, CA, USA; 8Service of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital, Lausanne, Switzerland; 9Sorbonne Universités, INSERM, UPMC Université Paris 06, Institut Pierre Louis d'Épidémiologie et de Santé Publique (IPLESP UMRS 1136), Paris, France; 10INSERM, CESP, U1018, Paris-Sud University, Le Kremlin-Bicêtre, France; 11Department of Internal Medicine, Bicêtre Hospital, AP-HP, Le Kremlin-Bicêtre, France; 12INSERM U1018, Centre de Recherche en Épidémiologie et Santé des Population, Paris-Sud University, Paris-Saclay University, Le Kremlin-Bicêtre, France; 13Division of Health Analytics, City of Hope Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, CA, USA; 14Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 15Service of Infectious Diseases, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; 16Department of Infectious Diseases, Bern University Hospital, University of Bern, Switzerland; 17Department of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel, Basel, Switzerland; 18Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital Olten, Olten, Switzerland; 19Division of Infectious Diseases, Cantonal Hospital of St. Gallen, St. Gallen, Switzerland; 20Division of Infectious Diseases, Regional Hospital of Lugano, Lugano, Switzerland; 21Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland; 22Institute of Medical Virology, University of Zurich, Zurich, Switzerland; 23JC Wilt Infectious Diseases Research Center, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada; 24Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada; 25Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA; 26CESP, UVSQ, INSERM, Université Paris-Saclay, Villejuif, France; 27Department of Hematology and Oncology, Hospital of Versailles, Le Chesnay, France and 28Precision Medicine Unit, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland.
ABSTRACT
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 popula- tion. In order to identify potential genetic risk loci, we performed case-con- trol genome-wide association studies and a meta-analysis across three cohorts of HIV-infected patients of European ancestry, including a total of 278 cases and 1,924 matched controls. We observed a significant associa- tion 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 popu- lation.
Correspondence:
JACQUES FELLAY
jacques.fellay@epfl.ch
Received: January 9, 2020. Accepted: July 14, 2020. Pre-published: July 16, 2020.
https://doi.org/10.3324/haematol.2020.247023
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