The impact of genetic ancestry on survival outcomes in pediatric rhabdomyosarcoma: A report from the Children’s Oncology Group

Emerging evidence suggests genetic ancestry may influence childhood cancer outcomes, but its impact on pediatric rhabdomyosarcoma (RMS) is unknown. We explored genetic ancestry's impact on survival among children with RMS. This multi-center observational cohort study is a secondary analysis of previously collected biobanking, genomic, and clinical data. The study included 920 individuals with newly diagnosed RMS under 40 years of age enrolled from 2005 to 2017 under the COG soft tissue sarcoma biobanking protocol D9902. The primary endpoints were (1) event-free survival (EFS), defined as the time from study enrollment to tumor recurrence/progression, secondary malignancy, or death from any cause; and (2) overall survival (OS), defined as the time from study enrollment to death from any cause. Genetic ancestry was estimated using Grafpop software, and Cox regression assessed the association between genetic ancestry and EFS and OS, considering RMS overall, by fusion status, and by histological subtype. Covariates included sex, age at diagnosis, tumor stage, and histology, except during stratified analyses. In embryonal RMS and PAX3/7:FOXO1 fusion-negative RMS, individuals with South Asian or Asian-Pacific Islander ancestry showed worse EFS (hazard ratio [HR] 2.06, 95% confidence interval [CI] 1.07-3.97, p = 0.03 and HR 2.01, 95% CI 1.07-3.76, p = 0.03, respectively) and OS (HR 2.30, 95% CI 1.09-4.84, p = 0.03 and HR 2.33, 95% CI 1.15-4.70, p = 0.020, respectively) compared to those with primarily European genetic ancestry. These findings suggest that genetic ancestry influences survival outcomes within RMS subtypes, and further understanding may improve precision-medicine-based efforts.

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Journal
Human Genetics and Genomics Advances
Published
2025-06-09
DOI
https://doi.org/10.1016/j.xhgg.2025.100466
Primary Topic
Sarcoma Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
0.00

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article

The impact of genetic ancestry on survival outcomes in pediatric rhabdomyosarcoma: A report from the Children’s Oncology Group

Mark Zobeck, Jack F. Shern, Michael E. Scheurer, Ekene Onwuka et al.
2 links
Human Genetics and Genomics Advances
Sarcoma Diagnosis and Treatment
article

The impact of genetic ancestry on survival outcomes in pediatric rhabdomyosarcoma: A report from the Children’s Oncology Group

Mark Zobeck, Jack F. Shern, Michael E. Scheurer, Ekene Onwuka, Brian D. Crompton, Erin R. Rudzinski, Christian Tibor Josef Magyar, Bailey A. Martin‐Giacalone, Donald A. Barkauskas, Deborah A. Marquez-Do, Elizabeth G. Atkinson, Corinne M. Linardic, Paul Scheet, Rajkumar Venkatramani, Chad D. Huff, Javed Khan, Philip J. Lupo, Michael Arnold, Melissa A. Richard, Douglas S. Hawkins, David Hall
article en

Abstract

Emerging evidence suggests genetic ancestry may influence childhood cancer outcomes, but its impact on pediatric rhabdomyosarcoma (RMS) is unknown. We explored genetic ancestry's impact on survival among children with RMS. This multi-center observational cohort study is a secondary analysis of previously collected biobanking, genomic, and clinical data. The study included 920 individuals with newly diagnosed RMS under 40 years of age enrolled from 2005 to 2017 under the COG soft tissue sarcoma biobanking protocol D9902. The primary endpoints were (1) event-free survival (EFS), defined as the time from study enrollment to tumor recurrence/progression, secondary malignancy, or death from any cause; and (2) overall survival (OS), defined as the time from study enrollment to death from any cause. Genetic ancestry was estimated using Grafpop software, and Cox regression assessed the association between genetic ancestry and EFS and OS, considering RMS overall, by fusion status, and by histological subtype. Covariates included sex, age at diagnosis, tumor stage, and histology, except during stratified analyses. In embryonal RMS and PAX3/7:FOXO1 fusion-negative RMS, individuals with South Asian or Asian-Pacific Islander ancestry showed worse EFS (hazard ratio [HR] 2.06, 95% confidence interval [CI] 1.07-3.97, p = 0.03 and HR 2.01, 95% CI 1.07-3.76, p = 0.03, respectively) and OS (HR 2.30, 95% CI 1.09-4.84, p = 0.03 and HR 2.33, 95% CI 1.15-4.70, p = 0.020, respectively) compared to those with primarily European genetic ancestry. These findings suggest that genetic ancestry influences survival outcomes within RMS subtypes, and further understanding may improve precision-medicine-based efforts.

Human Genetics and Genomics AdvancesVol. 6(3)
Children's Oncology Group (CH), Texas Medical Center (US), The University of Texas MD Anderson Cancer Center (US), Duke University (US), Baylor College of Medicine (US), Children's Hospital Colorado (US), Seattle Children's Hospital (US), Neurological Research Institute (US), Children's Oncology Group (US), National Cancer Institute (US), Children's Healthcare of Atlanta (US), Texas Children's Hospital (US), Center for Cancer Research (US), Children's Cancer Center (US), Department of Health and Human Services (US), Dana-Farber/Boston Children's Cancer and Blood Disorders Center (US), University of Colorado Denver (US)
Robert and Janice McNair Foundation, Cancer Prevention and Research Institute of Texas, St. Baldrick's Foundation, Foundation for Barnes-Jewish Hospital, Alvin J. Siteman Cancer Center, Children’s Oncology Group, National Human Genome Research Institute, National Cancer Institute, National Institute of General Medical Sciences
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