Sickle cell allele HBB-rs334(T) is associated with decreased risk of childhood Burkitt lymphoma in East Africa.

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  • Additional Information
    • Source:
      Publisher: Wiley-Blackwell Country of Publication: United States NLM ID: 7610369 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-8652 (Electronic) Linking ISSN: 03618609 NLM ISO Abbreviation: Am J Hematol Subsets: MEDLINE
    • Publication Information:
      Publication: New York Ny : Wiley-Blackwell
      Original Publication: New York, Liss.
    • Subject Terms:
      Burkitt Lymphoma*/epidemiology ; Burkitt Lymphoma*/genetics ; Malaria* ; Malaria, Falciparum*/epidemiology ; Malaria, Falciparum*/genetics ; Malaria, Falciparum*/complications ; Sickle Cell Trait*/epidemiology ; Sickle Cell Trait*/genetics ; Sickle Cell Trait*/complications; Humans ; Africa, Eastern ; Alleles ; Nectins/metabolism
    • Abstract:
      Burkitt lymphoma (BL) is an aggressive B-cell lymphoma that significantly contributes to childhood cancer burden in sub-Saharan Africa. Plasmodium falciparum, which causes malaria, is geographically associated with BL, but the evidence remains insufficient for causal inference. Inference could be strengthened by demonstrating that mendelian genes known to protect against malaria-such as the sickle cell trait variant, HBB-rs334(T)-also protect against BL. We investigated this hypothesis among 800 BL cases and 3845 controls in four East African countries using genome-scan data to detect polymorphisms in 22 genes known to affect malaria risk. We fit generalized linear mixed models to estimate odds ratios (OR) and 95% confidence intervals (95% CI), controlling for age, sex, country, and ancestry. The ORs of the loci with BL and P. falciparum infection among controls were correlated (Spearman's ρ = 0.37, p = .039). HBB-rs334(T) was associated with lower P. falciparum infection risk among controls (OR = 0.752, 95% CI 0.628-0.9; p = .00189) and BL risk (OR = 0.687, 95% CI 0.533-0.885; p = .0037). ABO-rs8176703(T) was associated with decreased risk of BL (OR = 0.591, 95% CI 0.379-0.992; p = .00271), but not of P. falciparum infection. Our results increase support for the etiological correlation between P. falciparum and BL risk.
      (© 2023 Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)
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    • Grant Information:
      Z01HG200362 United States HG NHGRI NIH HHS; Z01 HG200362 United States ImNIH Intramural NIH HHS; MC_UU_00033/1 United Kingdom MRC_ Medical Research Council; United States HH HHS; Z01 CP010176 United States ImNIH Intramural NIH HHS
    • Accession Number:
      0 (Nectins)
    • Publication Date:
      Date Created: 20231127 Date Completed: 20231227 Latest Revision: 20240726
    • Publication Date:
      20240726
    • Accession Number:
      PMC10872868
    • Accession Number:
      10.1002/ajh.27149
    • Accession Number:
      38009642