Communications Biology (Jan 2024)
Human leukocyte antigen-DQA1*04:01 and rs2040406 variants are associated with elevated risk of childhood Burkitt lymphoma
- Zhiwei Liu,
- Yang Luo,
- Samuel Kirimunda,
- Murielle Verboom,
- Olusegun O. Onabajo,
- Mateus H. Gouveia,
- Martin D. Ogwang,
- Patrick Kerchan,
- Steven J. Reynolds,
- Constance N. Tenge,
- Pamela A. Were,
- Robert T. Kuremu,
- Walter N. Wekesa,
- Nestory Masalu,
- Esther Kawira,
- Tobias Kinyera,
- Isaac Otim,
- Ismail D. Legason,
- Hadijah Nabalende,
- Herry Dhudha,
- Leona W. Ayers,
- Kishor Bhatia,
- James J. Goedert,
- Nathan Cole,
- Wen Luo,
- Jia Liu,
- Michelle Manning,
- Belynda Hicks,
- Ludmila Prokunina-Olsson,
- George Chagaluka,
- W. Thomas Johnston,
- Nora Mutalima,
- Eric Borgstein,
- George N. Liomba,
- Steve Kamiza,
- Nyengo Mkandawire,
- Collins Mitambo,
- Elizabeth M. Molyneux,
- Robert Newton,
- Ann W. Hsing,
- James E. Mensah,
- Anthony A. Adjei,
- Amy Hutchinson,
- Mary Carrington,
- Meredith Yeager,
- Rainer Blasczyk,
- Stephen J. Chanock,
- Soumya Raychaudhuri,
- Sam M. Mbulaiteye
Affiliations
- Zhiwei Liu
- Division of Cancer Epidemiology and Genetics, National Cancer Institute
- Yang Luo
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford
- Samuel Kirimunda
- College of Health Sciences, Makerere University
- Murielle Verboom
- Institute of Transfusion Medicine and Transplant Engineering
- Olusegun O. Onabajo
- Division of Cancer Epidemiology and Genetics, National Cancer Institute
- Mateus H. Gouveia
- Center for Research on Genomics & Global Health, NHGRI, National Institutes of Health
- Martin D. Ogwang
- St. Mary’s Hospital, Lacor
- Patrick Kerchan
- EMBLEM Study, African Field Epidemiology Network
- Steven J. Reynolds
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Constance N. Tenge
- EMBLEM Study, African Field Epidemiology Network
- Pamela A. Were
- EMBLEM Study, African Field Epidemiology Network
- Robert T. Kuremu
- EMBLEM Study, African Field Epidemiology Network
- Walter N. Wekesa
- EMBLEM Study, African Field Epidemiology Network
- Nestory Masalu
- Bugando Medical Center
- Esther Kawira
- EMBLEM Study, African Field Epidemiology Network
- Tobias Kinyera
- St. Mary’s Hospital, Lacor
- Isaac Otim
- St. Mary’s Hospital, Lacor
- Ismail D. Legason
- EMBLEM Study, African Field Epidemiology Network
- Hadijah Nabalende
- St. Mary’s Hospital, Lacor
- Herry Dhudha
- EMBLEM Study, African Field Epidemiology Network
- Leona W. Ayers
- Department of Pathology, The Ohio State University
- Kishor Bhatia
- Division of Cancer Epidemiology and Genetics, National Cancer Institute
- James J. Goedert
- Division of Cancer Epidemiology and Genetics, National Cancer Institute
- Nathan Cole
- Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research
- Wen Luo
- Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research
- Jia Liu
- Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research
- Michelle Manning
- Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research
- Belynda Hicks
- Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research
- Ludmila Prokunina-Olsson
- Division of Cancer Epidemiology and Genetics, National Cancer Institute
- George Chagaluka
- Departments of Pediatrics and Surgery, Kamuzu University of Health Sciences (formerly College of Medicine), University of Malawi
- W. Thomas Johnston
- Epidemiology and Cancer Statistics Group, Department of Health Sciences, University of York
- Nora Mutalima
- Epidemiology and Cancer Statistics Group, Department of Health Sciences, University of York
- Eric Borgstein
- Departments of Pediatrics and Surgery, Kamuzu University of Health Sciences (formerly College of Medicine), University of Malawi
- George N. Liomba
- Departments of Pediatrics and Surgery, Kamuzu University of Health Sciences (formerly College of Medicine), University of Malawi
- Steve Kamiza
- Departments of Pediatrics and Surgery, Kamuzu University of Health Sciences (formerly College of Medicine), University of Malawi
- Nyengo Mkandawire
- Departments of Pediatrics and Surgery, Kamuzu University of Health Sciences (formerly College of Medicine), University of Malawi
- Collins Mitambo
- National Health Sciences Research Committee, Research Department, Ministry of Health
- Elizabeth M. Molyneux
- Departments of Pediatrics and Surgery, Kamuzu University of Health Sciences (formerly College of Medicine), University of Malawi
- Robert Newton
- Epidemiology and Cancer Statistics Group, Department of Health Sciences, University of York
- Ann W. Hsing
- Stanford Cancer Institute, Stanford University
- James E. Mensah
- University of Ghana Medical School
- Anthony A. Adjei
- University of Ghana Medical School
- Amy Hutchinson
- Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research
- Mary Carrington
- Basic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD, USA and Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute
- Meredith Yeager
- Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research
- Rainer Blasczyk
- Institute of Transfusion Medicine and Transplant Engineering
- Stephen J. Chanock
- Division of Cancer Epidemiology and Genetics, National Cancer Institute
- Soumya Raychaudhuri
- Center for Data Sciences, Brigham and Women’s Hospital, Harvard Medical School
- Sam M. Mbulaiteye
- Division of Cancer Epidemiology and Genetics, National Cancer Institute
- DOI
- https://doi.org/10.1038/s42003-023-05701-5
- Journal volume & issue
-
Vol. 7,
no. 1
pp. 1 – 9
Abstract
Abstract Burkitt lymphoma (BL) is responsible for many childhood cancers in sub-Saharan Africa, where it is linked to recurrent or chronic infection by Epstein-Barr virus or Plasmodium falciparum. However, whether human leukocyte antigen (HLA) polymorphisms, which regulate immune response, are associated with BL has not been well investigated, which limits our understanding of BL etiology. Here we investigate this association among 4,645 children aged 0-15 years, 800 with BL, enrolled in Uganda, Tanzania, Kenya, and Malawi. HLA alleles are imputed with accuracy >90% for HLA class I and 85-89% for class II alleles. BL risk is elevated with HLA-DQA1*04:01 (adjusted odds ratio [OR] = 1.61, 95% confidence interval [CI] = 1.32-1.97, P = 3.71 × 10−6), with rs2040406(G) in HLA-DQA1 region (OR = 1.43, 95% CI = 1.26-1.63, P = 4.62 × 10−8), and with amino acid Gln at position 53 versus other variants in HLA-DQA1 (OR = 1.36, P = 2.06 × 10−6). The associations with HLA-DQA1*04:01 (OR = 1.29, P = 0.03) and rs2040406(G) (OR = 1.68, P = 0.019) persist in mutually adjusted models. The higher risk rs2040406(G) variant for BL is associated with decreased HLA-DQB1 expression in eQTLs in EBV transformed lymphocytes. Our results support the role of HLA variation in the etiology of BL and suggest that a promising area of research might be understanding the link between HLA variation and EBV control.
