Variation in the Human Leukocyte Antigen system and risk for endemic Burkitt lymphoma in northern Uganda.

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. Rare alleles 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 center dot 59, 95% CI 0 center dot 38-0 center dot 91), HLA-B*41 (aOR = 0 center dot 36, 95% CI 0 center dot 13-1 center dot 00), and HLA-B*58 alleles (aOR = 0 center dot 59, 95% CI 0 center dot 36-0 center dot 97). eBL cases had a lower frequency of HLA-DPB1 homozygosity (aOR = 0 center dot 57, 95% CI 0 center dot 40-0 center dot 82) but a higher frequency of HLA-DQA1 homozygosity (aOR = 2 center dot 19, 95% CI 1 center dot 42-3 center dot 37). Our results suggest that variation in HLA may be associated with eBL risk.