Onwuka Ekene A, Magyar Christina L, Martin-Giacalone Bailey A, Scheurer Michael E, Marquez-Do Deborah A, Zobeck Mark, Atkinson Elizabeth G, Rudzinski Erin R, Arnold Michael A, Barkauskas Donald A, Hall David, Khan Javed, Shern Jack F, Scheet Paul, Crompton Brian, Linardic Corinne M, Hawkins Douglas S, Venkatramani Rajkumar, Mirabello Lisa, Huff Chad D, Richard Melissa A, Lupo Philip J
Department of Pediatric Surgery, Surgical Oncology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
Graduate Program in Genetics and Genomics, Baylor College of Medicine, Houston, TX 77030, USA; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX 77030, USA; McNair Medical Institute, The Robert and Janice McNair Foundation, Houston, TX 77030, USA; Department of Pediatrics, Section of Hematology-Oncology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
HGG Adv. 2025 Jul 10;6(3):100466. doi: 10.1016/j.xhgg.2025.100466. Epub 2025 Jun 9.
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.
新出现的证据表明，遗传血统可能会影响儿童癌症的治疗结果，但其对小儿横纹肌肉瘤（RMS）的影响尚不清楚。我们探讨了遗传血统对RMS患儿生存的影响。这项多中心观察性队列研究是对先前收集的生物样本库、基因组和临床数据的二次分析。该研究纳入了920名2005年至2017年期间根据儿童肿瘤协作组（COG）软组织肉瘤生物样本库方案D9902入组的40岁以下新诊断为RMS的个体。主要终点为：（1）无事件生存期（EFS），定义为从研究入组到肿瘤复发/进展、继发性恶性肿瘤或任何原因导致的死亡的时间；（2）总生存期（OS），定义为从研究入组到任何原因导致的死亡的时间。使用Grafpop软件估计遗传血统，Cox回归评估遗传血统与EFS和OS之间的关联，总体上考虑RMS，按融合状态和组织学亚型进行分析。协变量包括性别、诊断时年龄、肿瘤分期和组织学，但分层分析时除外。在胚胎性RMS和PAX3/7:FOXO1融合阴性的RMS中，与主要具有欧洲遗传血统的个体相比，具有南亚或亚太岛民遗传血统的个体EFS（风险比[HR]分别为2.06，95%置信区间[CI]为1.07 - 3.97，p = 0.03；HR为2.01，95% CI为1.07 - 3.76，p = 0.03）和OS（HR分别为2.30，95% CI为1.09 - 4.84，p = 0.03；HR为2.33，95% CI为1.15 - 4.70，p = 0.020）较差。这些发现表明，遗传血统会影响RMS亚型的生存结果，进一步了解可能会改善基于精准医学的治疗效果。
