TY - JOUR
T1 - Variation in the Human Leukocyte Antigen system and risk for endemic Burkitt lymphoma in northern Uganda
AU - Kirimunda, Samuel
AU - Verboom, Murielle
AU - Otim, Isaac
AU - Ssennono, Mark
AU - Legason, Ismail D.
AU - Nabalende, Hadijah
AU - Ogwang, Martin D.
AU - Kerchan, Patrick
AU - Kinyera, Tobias
AU - Mwebaza, Ivan
AU - Joloba, Moses
AU - Ayers, Leona W.
AU - Reynolds, Steven J.
AU - Bhatia, Kishor
AU - Onabajo, Olusegun O.
AU - Hallensleben, Michael
AU - Biggar, Robert J.
AU - Prokunina-Olsson, Ludmila
AU - Goedert, James J.
AU - Blasczyk, Rainer
AU - Mbulaiteye, Sam M.
N1 - Funding Information:
We thank Ms. Janet Lawler‐Heavner at Westat Inc. (Rockville, MD, USA) and Mr. Erisa Sunday at the African Field Epidemiology Network (Kampala, Uganda) for managing the study. We are grateful to Mr. Wilson Nyegenye at the Uganda Bureau of Statistics (Kampala, Uganda) for training EMBLEM staff in field survey methods. We thank Ms. Laurie Buck, Dr. Carol Giffen, and Mr. Greg Rydzak at Information Management Services Inc. (Calverton, MD, USA) for coordinating data and preparing data analysis files. The work was funded by contracts from the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI) (Contracts HHSN261201100063C and HHSN261201100007I) and, in part, by the Intramural Research Program, National Institute of Allergy and Infectious Diseases (SJR), National Institutes of Health, Department of Health and Human Services, and by a Beginning Investigator Grant for Catalytic Research (BIG Cat) from the National Cancer Institute for African Scientists (US Civilian Research and Development Foundation [CRDF] Global award DAA3‐16‐62702 to SK) through a collaborative partnership between Makerere University’s College of Health Sciences and the Hannover Medical School’s Institute of Transfusion Medicine. The content of this manuscript is the sole responsibility of the authors, and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. The sponsors had no role in the study design, data collection, analysis, interpretation, writing of the manuscript, or the decision to submit the paper for publication. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Funding Information:
We thank Ms. Janet Lawler-Heavner at Westat Inc. (Rockville, MD, USA) and Mr. Erisa Sunday at the African Field Epidemiology Network (Kampala, Uganda) for managing the study. We are grateful to Mr. Wilson Nyegenye at the Uganda Bureau of Statistics (Kampala, Uganda) for training EMBLEM staff in field survey methods. We thank Ms. Laurie Buck, Dr. Carol Giffen, and Mr. Greg Rydzak at Information Management Services Inc. (Calverton, MD, USA) for coordinating data and preparing data analysis files. The work was funded by contracts from the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI) (Contracts HHSN261201100063C and HHSN261201100007I) and, in part, by the Intramural Research Program, National Institute of Allergy and Infectious Diseases (SJR), National Institutes of Health, Department of Health and Human Services, and by a Beginning Investigator Grant for Catalytic Research (BIG Cat) from the National Cancer Institute for African Scientists (US Civilian Research and Development Foundation [CRDF] Global award DAA3-16-62702 to SK) through a collaborative partnership between Makerere University’s College of Health Sciences and the Hannover Medical School’s Institute of Transfusion Medicine. The content of this manuscript is the sole responsibility of the authors, and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. The sponsors had no role in the study design, data collection, analysis, interpretation, writing of the manuscript, or the decision to submit the paper for publication. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Publisher Copyright:
© 2020 British Society for Haematology and John Wiley & Sons Ltd
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Endemic Burkitt lymphoma (eBL) is an aggressive childhood B-cell lymphoma associated with Plasmodium falciparum (Pf) malaria and Epstein–Barr virus (EBV) infections. Variation in the Human Leukocyte Antigen (HLA) system is suspected to play a role, but assessments using less accurate serology-based HLA typing techniques in small studies yielded conflicting results. We studied 200 eBL cases and 400 controls aged 0–15 years enrolled in northern Uganda and typed by accurate high-resolution HLA sequencing methods. HLA results were analyzed at one- or two-field resolution. Odds ratios and 95% confidence intervals (aOR, 95% CI) for eBL risk associated with common HLA alleles versus alleles that were rare ('1%) or differed by '2% between the cases and controls as the reference category, were estimated using multiple logistic regression adjusting for age, sex, microgeography, region, malaria positivity and treatment history, and genetic variants associated with eBL. Compared to the controls, eBL cases had a lower frequency of HLA-A*02 (aOR = 0·59, 95% CI 0·38–0·91), HLA-B*41 (aOR = 0·36, 95% CI 0·13–1·00), and HLA-B*58 alleles (aOR = 0·59, 95% CI 0·36–0·97). eBL cases had a lower frequency of HLA-DPB1 homozygosity (aOR = 0·57, 95% CI 0·40–0·82) but a higher frequency of HLA-DQA1 homozygosity (aOR = 2·19, 95% CI 1·42–3·37). Our results suggest that variation in HLA may be associated with eBL risk.
AB - Endemic Burkitt lymphoma (eBL) is an aggressive childhood B-cell lymphoma associated with Plasmodium falciparum (Pf) malaria and Epstein–Barr virus (EBV) infections. Variation in the Human Leukocyte Antigen (HLA) system is suspected to play a role, but assessments using less accurate serology-based HLA typing techniques in small studies yielded conflicting results. We studied 200 eBL cases and 400 controls aged 0–15 years enrolled in northern Uganda and typed by accurate high-resolution HLA sequencing methods. HLA results were analyzed at one- or two-field resolution. Odds ratios and 95% confidence intervals (aOR, 95% CI) for eBL risk associated with common HLA alleles versus alleles that were rare ('1%) or differed by '2% between the cases and controls as the reference category, were estimated using multiple logistic regression adjusting for age, sex, microgeography, region, malaria positivity and treatment history, and genetic variants associated with eBL. Compared to the controls, eBL cases had a lower frequency of HLA-A*02 (aOR = 0·59, 95% CI 0·38–0·91), HLA-B*41 (aOR = 0·36, 95% CI 0·13–1·00), and HLA-B*58 alleles (aOR = 0·59, 95% CI 0·36–0·97). eBL cases had a lower frequency of HLA-DPB1 homozygosity (aOR = 0·57, 95% CI 0·40–0·82) but a higher frequency of HLA-DQA1 homozygosity (aOR = 2·19, 95% CI 1·42–3·37). Our results suggest that variation in HLA may be associated with eBL risk.
KW - Burkitt lymphoma
KW - Epstein–Barr virus
KW - Plasmodium falciparum malaria
KW - epidemiology
KW - human leukocyte antigen
KW - non-Hodgkin lymphoma
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U2 - 10.1111/bjh.16398
DO - 10.1111/bjh.16398
M3 - Article
C2 - 32072624
AN - SCOPUS:85079715555
SN - 0007-1048
VL - 189
SP - 489
EP - 499
JO - British journal of haematology
JF - British journal of haematology
IS - 3
ER -