PMID- 38182727
OWN - NLM
STAT- MEDLINE
DCOM- 20240108
LR  - 20240214
IS  - 2399-3642 (Electronic)
IS  - 2399-3642 (Linking)
VI  - 7
IP  - 1
DP  - 2024 Jan 5
TI  - Human leukocyte antigen-DQA1*04:01 and rs2040406 variants are associated with 
      elevated risk of childhood Burkitt lymphoma.
PG  - 41
LID - 10.1038/s42003-023-05701-5 [doi]
LID - 41
AB  - 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 x 10(-6)), with rs2040406(G) in HLA-DQA1 
      region (OR = 1.43, 95% CI = 1.26-1.63, P = 4.62 x 10(-8)), and with amino acid 
      Gln at position 53 versus other variants in HLA-DQA1 (OR = 1.36, 
      P = 2.06 x 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.
CI  - (c) 2024. This is a U.S. Government work and not under copyright protection in the 
      US; foreign copyright protection may apply.
FAU - Liu, Zhiwei
AU  - Liu Z
AUID- ORCID: 0000-0002-0136-651X
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, MD, USA.
FAU - Luo, Yang
AU  - Luo Y
AUID- ORCID: 0000-0001-7385-6166
AD  - Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, 
      Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
AD  - Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
AD  - Division of Rheumatology, Immunology, and Immunity, Brigham and Women's Hospital, 
      Harvard Medical School, Boston, MA, USA.
AD  - Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
AD  - Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
FAU - Kirimunda, Samuel
AU  - Kirimunda S
AD  - College of Health Sciences, Makerere University, Kampala, Uganda.
FAU - Verboom, Murielle
AU  - Verboom M
AD  - Institute of Transfusion Medicine and Transplant Engineering, Hanover, Germany.
FAU - Onabajo, Olusegun O
AU  - Onabajo OO
AUID- ORCID: 0000-0001-6342-2380
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, MD, USA.
FAU - Gouveia, Mateus H
AU  - Gouveia MH
AUID- ORCID: 0000-0001-6711-5265
AD  - Center for Research on Genomics & Global Health, NHGRI, National Institutes of 
      Health, Bethesda, MD, USA.
FAU - Ogwang, Martin D
AU  - Ogwang MD
AD  - St. Mary's Hospital, Lacor, Gulu, Uganda.
AD  - EMBLEM Study, African Field Epidemiology Network, Kampala, Uganda.
FAU - Kerchan, Patrick
AU  - Kerchan P
AD  - EMBLEM Study, African Field Epidemiology Network, Kampala, Uganda.
AD  - Kuluva Hospital, Arua, Uganda.
FAU - Reynolds, Steven J
AU  - Reynolds SJ
AD  - Division of Intramural Research, National Institute of Allergy and Infectious 
      Diseases, National Institutes of Health, Bethesda, MD, USA.
FAU - Tenge, Constance N
AU  - Tenge CN
AD  - EMBLEM Study, African Field Epidemiology Network, Kampala, Uganda.
AD  - Moi University College of Health Sciences, Eldoret, Kenya.
FAU - Were, Pamela A
AU  - Were PA
AD  - EMBLEM Study, African Field Epidemiology Network, Kampala, Uganda.
AD  - Academic Model Providing Access To Healthcare (AMPATH), Eldoret, Kenya.
FAU - Kuremu, Robert T
AU  - Kuremu RT
AD  - EMBLEM Study, African Field Epidemiology Network, Kampala, Uganda.
AD  - Moi University College of Health Sciences, Eldoret, Kenya.
FAU - Wekesa, Walter N
AU  - Wekesa WN
AD  - EMBLEM Study, African Field Epidemiology Network, Kampala, Uganda.
AD  - Moi University College of Health Sciences, Eldoret, Kenya.
FAU - Masalu, Nestory
AU  - Masalu N
AD  - Bugando Medical Center, Mwanza, Tanzania.
FAU - Kawira, Esther
AU  - Kawira E
AD  - EMBLEM Study, African Field Epidemiology Network, Kampala, Uganda.
AD  - Shirati Health, Education, and Development Foundation, Shirati, Tanzania.
FAU - Kinyera, Tobias
AU  - Kinyera T
AD  - St. Mary's Hospital, Lacor, Gulu, Uganda.
AD  - EMBLEM Study, African Field Epidemiology Network, Kampala, Uganda.
FAU - Otim, Isaac
AU  - Otim I
AD  - St. Mary's Hospital, Lacor, Gulu, Uganda.
AD  - EMBLEM Study, African Field Epidemiology Network, Kampala, Uganda.
FAU - Legason, Ismail D
AU  - Legason ID
AUID- ORCID: 0000-0002-6118-542X
AD  - EMBLEM Study, African Field Epidemiology Network, Kampala, Uganda.
AD  - Kuluva Hospital, Arua, Uganda.
FAU - Nabalende, Hadijah
AU  - Nabalende H
AD  - St. Mary's Hospital, Lacor, Gulu, Uganda.
AD  - EMBLEM Study, African Field Epidemiology Network, Kampala, Uganda.
FAU - Dhudha, Herry
AU  - Dhudha H
AD  - EMBLEM Study, African Field Epidemiology Network, Kampala, Uganda.
AD  - Shirati Health, Education, and Development Foundation, Shirati, Tanzania.
FAU - Ayers, Leona W
AU  - Ayers LW
AD  - Department of Pathology, The Ohio State University, Columbus, OH, USA.
FAU - Bhatia, Kishor
AU  - Bhatia K
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, MD, USA.
FAU - Goedert, James J
AU  - Goedert JJ
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, MD, USA.
FAU - Cole, Nathan
AU  - Cole N
AD  - Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer 
      Research, Frederick, MD, USA.
FAU - Luo, Wen
AU  - Luo W
AD  - Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer 
      Research, Frederick, MD, USA.
FAU - Liu, Jia
AU  - Liu J
AD  - Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer 
      Research, Frederick, MD, USA.
FAU - Manning, Michelle
AU  - Manning M
AD  - Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer 
      Research, Frederick, MD, USA.
FAU - Hicks, Belynda
AU  - Hicks B
AUID- ORCID: 0000-0001-8014-4888
AD  - Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer 
      Research, Frederick, MD, USA.
FAU - Prokunina-Olsson, Ludmila
AU  - Prokunina-Olsson L
AUID- ORCID: 0000-0002-9622-2091
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, MD, USA.
FAU - Chagaluka, George
AU  - Chagaluka G
AD  - Departments of Pediatrics and Surgery, Kamuzu University of Health Sciences 
      (formerly College of Medicine), University of Malawi, Blantyre, Malawi.
FAU - Johnston, W Thomas
AU  - Johnston WT
AD  - Epidemiology and Cancer Statistics Group, Department of Health Sciences, 
      University of York, York, UK.
FAU - Mutalima, Nora
AU  - Mutalima N
AD  - Epidemiology and Cancer Statistics Group, Department of Health Sciences, 
      University of York, York, UK.
AD  - Cancer Epidemiology Unit, University of Oxford, Oxford, UK.
FAU - Borgstein, Eric
AU  - Borgstein E
AD  - Departments of Pediatrics and Surgery, Kamuzu University of Health Sciences 
      (formerly College of Medicine), University of Malawi, Blantyre, Malawi.
FAU - Liomba, George N
AU  - Liomba GN
AD  - Departments of Pediatrics and Surgery, Kamuzu University of Health Sciences 
      (formerly College of Medicine), University of Malawi, Blantyre, Malawi.
FAU - Kamiza, Steve
AU  - Kamiza S
AD  - Departments of Pediatrics and Surgery, Kamuzu University of Health Sciences 
      (formerly College of Medicine), University of Malawi, Blantyre, Malawi.
FAU - Mkandawire, Nyengo
AU  - Mkandawire N
AD  - Departments of Pediatrics and Surgery, Kamuzu University of Health Sciences 
      (formerly College of Medicine), University of Malawi, Blantyre, Malawi.
FAU - Mitambo, Collins
AU  - Mitambo C
AD  - National Health Sciences Research Committee, Research Department, Ministry of 
      Health, Lilongwe, Malawi.
FAU - Molyneux, Elizabeth M
AU  - Molyneux EM
AD  - Departments of Pediatrics and Surgery, Kamuzu University of Health Sciences 
      (formerly College of Medicine), University of Malawi, Blantyre, Malawi.
FAU - Newton, Robert
AU  - Newton R
AUID- ORCID: 0000-0001-6715-9153
AD  - Epidemiology and Cancer Statistics Group, Department of Health Sciences, 
      University of York, York, UK.
FAU - Hsing, Ann W
AU  - Hsing AW
AD  - Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
FAU - Mensah, James E
AU  - Mensah JE
AD  - University of Ghana Medical School, Accra, Ghana.
FAU - Adjei, Anthony A
AU  - Adjei AA
AD  - University of Ghana Medical School, Accra, Ghana.
FAU - Hutchinson, Amy
AU  - Hutchinson A
AD  - Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer 
      Research, Frederick, MD, USA.
FAU - Carrington, Mary
AU  - Carrington M
AUID- ORCID: 0000-0002-2692-2180
AD  - 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, 
      Bethesda, MD, USA.
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
FAU - Yeager, Meredith
AU  - Yeager M
AUID- ORCID: 0000-0003-3871-2225
AD  - Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer 
      Research, Frederick, MD, USA.
FAU - Blasczyk, Rainer
AU  - Blasczyk R
AUID- ORCID: 0000-0003-3875-3190
AD  - Institute of Transfusion Medicine and Transplant Engineering, Hanover, Germany.
FAU - Chanock, Stephen J
AU  - Chanock SJ
AUID- ORCID: 0000-0002-2324-3393
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, MD, USA.
FAU - Raychaudhuri, Soumya
AU  - Raychaudhuri S
AUID- ORCID: 0000-0002-1901-8265
AD  - Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
AD  - Division of Rheumatology, Immunology, and Immunity, Brigham and Women's Hospital, 
      Harvard Medical School, Boston, MA, USA.
AD  - Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
AD  - Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
FAU - Mbulaiteye, Sam M
AU  - Mbulaiteye SM
AUID- ORCID: 0000-0002-8273-9831
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, MD, USA. mbulaits@mail.nih.gov.
LA  - eng
GR  - HHSN261201100007C/HL/NHLBI NIH HHS/United States
GR  - HHSN261201100007I/CA/NCI NIH HHS/United States
GR  - HHSN261201100063C/CA/NCI NIH HHS/United States
GR  - MC_UU_00033/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20240105
PL  - England
TA  - Commun Biol
JT  - Communications biology
JID - 101719179
RN  - 0 (HLA-DQA1 antigen)
RN  - 0 (HLA-DQ alpha-Chains)
SB  - IM
MH  - Child
MH  - Humans
MH  - *Burkitt Lymphoma/genetics
MH  - *Epstein-Barr Virus Infections/complications/genetics
MH  - Herpesvirus 4, Human/genetics
MH  - HLA-DQ alpha-Chains/genetics
PMC - PMC10770398
COIS- The authors declare no competing interests.
EDAT- 2024/01/06 10:42
MHDA- 2024/01/08 06:43
PMCR- 2024/01/05
CRDT- 2024/01/05 23:29
PHST- 2023/06/21 00:00 [received]
PHST- 2023/12/12 00:00 [accepted]
PHST- 2024/01/08 06:43 [medline]
PHST- 2024/01/06 10:42 [pubmed]
PHST- 2024/01/05 23:29 [entrez]
PHST- 2024/01/05 00:00 [pmc-release]
AID - 10.1038/s42003-023-05701-5 [pii]
AID - 5701 [pii]
AID - 10.1038/s42003-023-05701-5 [doi]
PST - epublish
SO  - Commun Biol. 2024 Jan 5;7(1):41. doi: 10.1038/s42003-023-05701-5.