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 of 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.
