Journal
BLOOD ADVANCES
Volume 5, Issue 2, Pages 451-458Publisher
ELSEVIER
DOI: 10.1182/bloodadvances.2020003060
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Funding
- National Cancer Institute (NCI)
- National Institutes of Health [R03CA223730]
- Rally Foudation
- Roswell Park Alliance Foundation
- KL2 Mentored Career Development Award from the Irving Institute for Clinical and Translational Research at Columbia University Irving Medical Center [KL2-TR001874]
- Cancer Center Support Grant
- NCI [P30 CA16056]
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This study found that Black and Hispanic children treated for ALL have a lower risk of bone toxicities, partly due to the percentage of African ancestry in their genetic admixture. Meanwhile, patients with a higher percentage of Native American ancestry showed significantly poorer overall survival and event-free survival.
Hispanic children have a higher incidence of acute lymphoblastic leukemia (ALL) and inferior treatment outcomes relative to non-Hispanic White children. We previously reported that Hispanic children with ALL had lower risk of fracture and osteonecrosis. To unravel the genetic root of such ethnic differences, we genotyped 449 patients from the DFCI 05-001 cohort and analyzed their ancestry. Patients with discordant clinical and genetic ancestral groups were reclassified, and those with unknown ancestry were reassigned on the basis of genetic estimates. Both clinical and genetic ancestries were analyzed in relation to risk of bone toxicities and survival outcomes. Consistent with clinically reported race/ethnicity, genetically defined Hispanic and Black patients had significantly lower risk of fracture (Hispanic: subdistribution hazard ratio [SHR], 0.42; 95% confidence interval [CI], 0.22-0.81; P = .01; Black: SHR, 0.28; 95% CI, 0.10-0.75; P = .01), and osteonecrosis (Hispanic: SHR, 0.12; 95% CI, 0.02-0.93; P = .04; Black: SHR, 0.24; 95% CI, 0.08-0.78; P = .02). The lower risk was driven by African but not Native American or Asian ancestry. In addition, patients with a higher percentage of Native American ancestry had significantly poorer overall survival and event-free survival. Our study revealed that the lower risk of bone toxicities among Black and Hispanic children treated for ALL was attributed, in part, to the percentage of African ancestry in their genetic admixture. The findings provide suggestive evidence for the protective effects of genetic factors associated with African decent against bone damage caused by ALL treatment and clues for future studies to identify underlying biological mechanisms.
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