Human leukocyte antigen-DQA1*04:01 and rs2040406 variants are associated with elevated risk of childhood Burkitt lymphoma
Liu, Zhiwei; Luo, Yang; Kirimunda, Samuel; Verboom, Murielle; Onabajo, lusegun O.; Gouveia, Mateus H.; Ogwang, Martin D.; Kerchan, Patrick; Reynolds, Steven J.; Tenge, Constance N; Were, Pamela A.; Kuremu, Robert T.; Wekesa, Walter N.; Masalu, Nestory; Kawira, Esther; Kinyera, Tobias; Otim, Isaac; Legason, Ismail D; Nabalende, Hadijah; Dhudha, Herry; Ayers, Leona W.; Bhatia, Kishor; Goedert, James J.; Cole, Nathan; Luo, Wen; Liu, Jia; Manning, Michelle; Hicks, Belynda; Prokunina-Olsson, Ludmila; Chagaluka, George; Johnston, W. Thomas J; Mutalima, Nora; Borgstein, Eric; Liomba, George N.; Kamiza, Steve; Mkandawire, Nyengo; Mitambo, Collins; Molyneux, Elizabeth M; Newton, , Robert; Hsing, Ann W.; . Mensah, James E; Adjei, Anthony A.; Hutchinson, Amy; Carrington, Mary; Yeage, Meredith; Blasczyk, Rainer; . Chanock, Stephen J; Raychaudhuri, Soumya; Mbulaiteye, Sam M.
Date:
2024-01-05
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 reg-
ulate 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 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.
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