Genetic ancestry, differential gene expression, and survival in pediatric B-cell acute lymphoblastic leukemia.
Genetic ancestry, differential gene expression, and survival in pediatric B-cell acute lymphoblastic leukemia.
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DOI：
10.1002/cam4.5266
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发表时间：
2023-02
期刊：
影响因子：
4
通讯作者：
Williams LA
中科院分区：
文献类型：
--
作者：
Barragan FA;Mills LJ;Raduski AR;Marcotte EL;Grinde KE;Spector LG;Williams LA
与白色和拉丁裔儿童相比，黑人儿童的B-细胞急性淋巴细胞白血病（B-ALL）发病率较低，但生存率较差。在考虑与遗传祖先相关的差异表达基因后，尚不清楚报告的人种/种族（RRE）与B‐ALL死亡的相关性。使用I期和II期NCI TARGET B-ALL病例（N = 273; RRE-黑人= 21，RRE-白色= 162，RRE-Latinx = 69，RRE-其他= 9，RRE-未知= 12），我们估计了非洲人（AFR）、欧洲人（EUR）和美洲印第安人（AMR）遗传血统的比例。我们估计了血统和死亡之间的风险比（HR）和95%置信区间（95%CI），同时调整了RRE和临床指标。我们确定了与遗传祖先相关的基因，并在RRE和死亡关联中对其进行了调整。RRE内的遗传血统不同（RRE-黑人，AFR比例：平均值：78.5%，范围：38.2%-93.6%; RRE-白色，EUR比例：平均值：94%，范围：1.6%-99.9%; RRE-拉丁裔，AMR比例：平均值：52.0%，范围：1.2%-98.7%）。我们分别鉴定了10个、1个和6个与AFR、AMR和EUR血统比例相关的差异表达基因（p校正<0.05）。我们发现AMR和AFR血统与死亡统计学显著相关（AMR每增加10% HR：1.05，95% CI：1.03-1.17，AFR每增加10% HR：1.03，95% CI：1.01-1.19）。在调整与RRE-黑人儿童的遗传祖先相关的基因后，RRE-拉丁裔儿童的死亡风险差异幅度更大，但RRE-拉丁裔儿童的差异不明显（RRE-黑人HR：3.35，95% CI：1.31，8.53; RRE-拉丁裔HR：1.47，0.88-2.45）。我们的工作强调了在调整祖先差异表达基因后RRE的B‐ALL生存差异，表明影响生存的其他因素也很重要。利用基因型、基因表达和生存数据，我们分析了儿童B-细胞急性淋巴细胞白血病（B-ALL）中人种/种族与生存之间的关系，并考虑了与遗传祖先相关的基因。我们的研究结果表明，遗传祖先及其相关基因在B‐ALL中种族/民族差异的发生和程度中发挥着有意义的作用。
Black children have lower incidence yet worse survival than White and Latinx children with B‐cell acute lymphoblastic leukemia (B‐ALL). It is unclear how reported race/ethnicity (RRE) is associated with death in B‐ALL after accounting for differentially expressed genes associated with genetic ancestry. Using Phase 1 and 2 NCI TARGET B‐ALL cases (N = 273; RRE‐Black = 21, RRE‐White = 162, RRE‐Latinx = 69, RRE‐Other = 9, RRE‐Unknown = 12), we estimated proportions of African (AFR), European (EUR), and Amerindian (AMR) genetic ancestry. We estimated hazard ratios (HR) and 95% confidence intervals (95% CI) between ancestry and death while adjusting for RRE and clinical measures. We identified genes associated with genetic ancestry and adjusted for them in RRE and death associations. Genetic ancestry varied within RRE (RRE‐Black, AFR proportion: Mean: 78.5%, Range: 38.2%–93.6%; RRE‐White, EUR proportion: Mean: 94%, Range: 1.6%–99.9%; RRE‐Latinx, AMR proportion: Mean: 52.0%, Range: 1.2%–98.7%). We identified 10, 1, and 6 differentially expressed genes (p adjusted <0.05) associated with AFR, AMR, and EUR ancestry proportion, respectively. We found AMR and AFR ancestry were statistically significantly associated with death (AMR each 10% HR: 1.05, 95% CI: 1.03–1.17, AFR each 10% increase HR: 1.03, 95% CI:1.01–1.19). RRE differences in the risk of death were larger in magnitude upon adjustment for genes associated with genetic ancestry for RRE‐Black, but not RRE‐Latinx children (RRE‐Black HR: 3.35, 95% CI: 1.31, 8.53; RRE‐Latinx HR: 1.47, 0.88–2.45). Our work highlights B‐ALL survival differences by RRE after adjusting for ancestry differentially expressed genes suggesting other factors impacting survival are important. Using genotype, gene expression, and survival data, we analyzed the relationship between race/ethnicity and survival in pediatric B‐cell acute lymphoblastic leukemia (B‐ALL), when accounting for genes associated with genetic ancestry. Our results suggest that genetic ancestry and its associated genes play meaningful roles in the occurrence and magnitude of racial/ethnic disparities in B‐ALL.
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