Variation in the Human Leukocyte Antigen system and risk for endemic Burkitt lymphoma in northern Uganda
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Date
2020
Journal Title
Journal ISSN
Volume Title
Publisher
British journal of haematology
Abstract
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.
Description
Keywords
Burkitt lymphoma, Non-Hodgkin lymphoma, Epidemiology, Epstein– Barr virus, Plasmodium falciparum malaria, Human leukocyte antigen
Citation
Kirimunda, S., Verboom, M., Otim, I., Ssennono, M., Legason, I. D., Nabalende, H., ... & Mbulaiteye, S. M. (2020). Variation in the Human Leukocyte Antigen system and risk for endemic Burkitt lymphoma in northern Uganda. British journal of haematology, 189(3), 489-499. doi: 10.1111/bjh.16398