Evidence map›Paper›PMID 36951526›Full record

ArticleJournal of the National Cancer Institute2023

Germline genetic variants and pediatric rhabdomyosarcoma outcomes: a report from the Children's Oncology Group.

Bailey A Martin-Giacalone, Melissa A Richard, Michael E Scheurer, Javed Khan, Pagna Sok, Priya B Shetty, Stephen J Chanock, Shengchao Alfred Li, Meredith Yeager, Deborah A Marquez-Do and 12 more

Open access · greenAbstract read
In one paragraph

Article in Journal of the National Cancer Institute, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.0field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Observational
  3. Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 8 institutions in 1 country.

Bailey A Martin-GiacaloneDivision of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.ORCID 0000-0003-0758-8487
Melissa A RichardSection of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Michael E ScheurerSection of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Javed KhanGenetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Pagna SokSection of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Priya B ShettySection of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Stephen J ChanockDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Shengchao Alfred LiFrederick National Laboratory for Cancer Research, Frederick, MD, USA.
Meredith YeagerFrederick National Laboratory for Cancer Research, Frederick, MD, USA.
Deborah A Marquez-DoSection of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Donald A BarkauskasDepartment of Population and Public Health Sciences, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.ORCID 0000-0002-2339-719X
David HallQuadW Childhood Sarcoma Biostatistics and Annotation Office, Children's Oncology Group, Monrovia, CA, USA.ORCID 0000-0003-1257-2316
Matthew T McEvoySection of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Austin L BrownSection of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Aniko SaboHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.ORCID 0000-0002-9667-8072
Paul ScheetDepartment of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Chad D HuffDepartment of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Stephen X SkapekDepartment of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Douglas S HawkinsDivision of Hematology-Oncology, Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.ORCID 0000-0003-3602-1375
Rajkumar VenkatramaniSection of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Lisa MirabelloClinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MA, USA.
Philip J LupoSection of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.ORCID 0000-0003-0978-5863
Baylor College of Medicine · USNational Institutes of Health · USFrederick National Laboratory for Cancer Research · USThe University of Texas MD Anderson Cancer Center · USChildren's Oncology Group · USSeattle Children's Hospital · USThe University of Texas Southwestern Medical Center · USUniversity of Southern California · US

Funding

NCTN BIQSFP ANBL1531 (NRT)U10CA180886 · NCI · PUBLIC HEALTH INSTITUTE · PI Douglas S. Hawkins · 2014 to 2026
$390.6M
COG FOREIGN ACCRUALU10CA098543 · NCI · NATIONAL CHILDHOOD CANCER FOUNDATION · PI ADAMSON, PETER C. · 2003 to 2013
$335.5M
COG SDMC - Statistics CoreU10CA180899 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI TODD A ALONZO · 2014 to 2026
$132.8M
Children's Oncology Group Statistics &Data Center GrantU10CA098413 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI ANDERSON, JAMES R · 2003 to 2013
$67.5M
MEDICAL GENETICS RESEARCH FELLOWSHIP PROGRAMT32GM007526 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI Brendan Lee · 1985 to 2026
$11.4M
BIOINFORMATICS: SYSTEMS BIOLOGY OF PEDIATRIC CANCERSZIABC011002 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KHAN, JAVED · 2009 to 2025
$9.3M
Postdoctoral Training in Cancer Prevention and ControlT32CA190194 · NCI · WASHINGTON UNIVERSITY · PI GRAHAM A. COLDITZ, AIMEE S JAMES · 2014 to 2026
$4.7M
Predicting Response Prognosis in Pediatric CancersZIASC010366 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI KHAN, JAVED · 2009 to 2025
$4.7M
Training Program in Translational Biology and Molecular MedicineT32GM088129 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI ROONEY, CLIONA M., VAN DEN VEYVER, IGNATIA B · 2010 to 2019
$3.0M
NCI NIH HHS T32 CA190194NCI NIH HHS T32CA190194NCI NIH HHS U10 CA098413NCI NIH HHS U10 CA098543NCI NIH HHS U10 CA180886NCI NIH HHS U10 CA180899NIGMS NIH HHS T32 GM007526NIGMS NIH HHS T32 GM088129NIGMS NIH HHS T32GM088129
6 · The paper itself

Abstract

backgroundRelative to other pediatric cancers, survival for rhabdomyosarcoma (RMS) has not improved in recent decades, suggesting the need to enhance risk stratification. Therefore, we conducted a genome-wide association study for event-free survival (EFS) and overall survival (OS) to identify genetic variants associated with outcomes in individuals with RMS.

methodsThe study included 920 individuals with newly diagnosed RMS who were enrolled in Children's Oncology Group protocols. To assess the association of each single nucleotide polymorphism (SNP) with EFS and OS, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) using multivariable Cox proportional hazards models, adjusted for clinical covariates. All statistical tests were two sided. We also performed stratified analyses by histological subtype (alveolar and embryonal RMS) and carried out sensitivity analyses of statistically significant SNPs by PAX3/7-FOXO1 fusion status and genetic ancestry group.

resultsWe identified that rs17321084 was associated with worse EFS (HR = 2.01, 95% CI = 1.59 to 2.53, P = 5.39 × 10-9) and rs10094840 was associated with worse OS (HR = 1.84, 95% CI = 1.48 to 2.27, P = 2.13 × 10-8). Using publicly available data, we found that rs17321084 lies in a binding region for transcription factors GATA2 and GATA3, and rs10094840 is associated with SPAG1 and RNF19A expression. We also identified that CTNNA3 rs2135732 (HR = 3.75, 95% CI = 2.34 to 5.99, P = 3.54 × 10-8) and MED31 rs74504320 (HR = 3.21, 95% CI = 2.12 to 4.86, P = 3.60 × 10-8) were associated with worse OS among individuals with alveolar RMS.

conclusionsWe demonstrated that common germline variants are associated with EFS and OS among individuals with RMS. Additional replication and investigation of these SNP effects may further support their consideration in risk stratification protocols.

Indexed as

RhabdomyosarcomaRhabdomyosarcoma, AlveolarChildGenome-Wide Association StudyGerm CellsHumansMediator ComplexProportional Hazards ModelsUbiquitin-Protein LigasesMED31 protein, humanMediator ComplexRNF19A protein, humanUbiquitin-Protein Ligases

Identifiers

PMID36951526
PMCPMC10248851
OpenAlexW4353114519

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