Open AccessGenetic ancestry, differential gene expression, and survival in pediatric B‐cell acute lymphoblastic leukemia
Author(s) -
Barragan Freddy A.,
Mills Lauren J.,
Raduski Andrew R.,
Marcotte Erin L.,
Grinde Kelsey E.,
Spector Logan G.,
Williams Lindsay A.
Publication year - 2023
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.5266
Subject(s) - hazard ratio , confidence interval , genetic genealogy , demography , medicine , gene , genetics , biology , population , environmental health , sociology
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.