Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA.
Center for Research on Genomics and Global Health, NHGRI, National Institutes of Health, Bethesda, Maryland, USA.
Am J Hematol. 2024 Jan;99(1):113-123. doi: 10.1002/ajh.27149. Epub 2023 Nov 27.
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.
伯基特淋巴瘤（BL）是一种侵袭性 B 细胞淋巴瘤，在撒哈拉以南非洲地区对儿童癌症负担有重大影响。导致疟疾的疟原虫与 BL 在地理上相关，但因果关系的证据仍然不足。如果能够证明已知对抗疟疾的孟德尔基因（如镰状细胞特征变体 HBB-rs334(T)-T）也能对抗 BL，那么这一推断可以得到加强。我们使用全基因组扫描数据，在东非的四个国家对 800 例 BL 病例和 3845 例对照进行了研究，以检测已知影响疟疾风险的 22 个基因中的多态性。我们拟合了广义线性混合模型，以估计比值比（OR）和 95%置信区间（95%CI），并控制了年龄、性别、国家和祖先。与 BL 和疟原虫感染相关的基因座在对照人群中的 OR 呈正相关（Spearman ρ=0.37，p=0.039）。HBB-rs334(T)与对照人群中较低的疟原虫感染风险相关（OR=0.752，95%CI 0.628-0.9；p=0.00189）和 BL 风险（OR=0.687，95%CI 0.533-0.885；p=0.0037）。ABO-rs8176703(T)与 BL 风险降低相关（OR=0.591，95%CI 0.379-0.992；p=0.00271），但与疟原虫感染无关。我们的结果增加了对疟原虫与 BL 风险之间病因相关性的支持。
