Genetic ancestry, differential gene expression, and survival in pediatric B-cell acute lymphoblastic leukemia

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Abstract

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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).

CONCLUSIONS: Our work highlights B-ALL survival differences by RRE after adjusting for ancestry differentially expressed genes suggesting other factors impacting survival are important.

Original languageEnglish (US)
JournalCancer medicine
DOIs
StateAccepted/In press - 2022

Bibliographical note

Funding Information:
This work was supported by the National Cancer Institute of the National Institutes of Health under Award Number 1R01CA239701‐01A1S1 (PI: LGS; Trainee: FB). This work is also supported by the Children's Cancer Research Fund and the Department of Defense (W81XWH‐21‐1‐0397; LAW).

Publisher Copyright:
© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Keywords

  • acute lymphoblastic leukemia
  • genetic ancestry
  • survival disparities

PubMed: MeSH publication types

  • Journal Article

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