Evidence map›Paper›PMID 38871555›Full record

ArticleCancer epidemiology2024

Genetic variation near GRB10 associated with bone growth and osteosarcoma risk in canine and human populations.

Sydney E Lucas, Tianzhong Yang, Courtney E Wimberly, Kajal V Parmar, Helen M Hansen, Adam J de Smith, Libby M Morimoto, Catherine Metayer, Quinn T Ostrom, William C Eward and 5 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer epidemiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Review
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

15 authors.

Sydney E LucasPreston Robert Tisch Brain Tumor Center, Department of Neurosurgery, Duke University, Durham, NC, USA; Division of Pediatric Hematology/Oncology, Duke University Medical Center, Durham, NC, USA.
Tianzhong YangDivision of Biostatistics and Health Data Science, School of Public Health, University of Minnesota, Minneapolis, MN, USA; Division of Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA; Division of Pediatric Hematology/Oncology, Duke University Medical Center, Durham, NC, USA.
Courtney E WimberlyPreston Robert Tisch Brain Tumor Center, Department of Neurosurgery, Duke University, Durham, NC, USA; Division of Pediatric Hematology/Oncology, Duke University Medical Center, Durham, NC, USA.
Kajal V ParmarPreston Robert Tisch Brain Tumor Center, Department of Neurosurgery, Duke University, Durham, NC, USA; Division of Pediatric Hematology/Oncology, Duke University Medical Center, Durham, NC, USA.
Helen M HansenDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA; Division of Pediatric Hematology/Oncology, Duke University Medical Center, Durham, NC, USA.
Adam J de SmithCenter for Genetic Epidemiology, Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA; Division of Pediatric Hematology/Oncology, Duke University Medical Center, Durham, NC, USA.
Libby M MorimotoSchool of Public Health, University of California, Berkeley, Berkeley, CA, USA; Division of Pediatric Hematology/Oncology, Duke University Medical Center, Durham, NC, USA.
Catherine MetayerSchool of Public Health, University of California, Berkeley, Berkeley, CA, USA; Division of Pediatric Hematology/Oncology, Duke University Medical Center, Durham, NC, USA.
Quinn T OstromPreston Robert Tisch Brain Tumor Center, Department of Neurosurgery, Duke University, Durham, NC, USA; Duke Cancer Institute, Duke University, Durham, NC, USA; Division of Pediatric Hematology/Oncology, Duke University Medical Center, Durham, NC, USA.
William C EwardDuke Cancer Institute, Duke University, Durham, NC, USA; Department of Orthopaedic Surgery, Duke University, Durham, NC, USA; Division of Pediatric Hematology/Oncology, Duke University Medical Center, Durham, NC, USA.
Laurie A GravesDepartment of Pediatrics, Duke University, Durham, NC, USA; Division of Pediatric Hematology/Oncology, Duke University Medical Center, Durham, NC, USA.
Lars M WagnerDuke Cancer Institute, Duke University, Durham, NC, USA; Department of Pediatrics, Duke University, Durham, NC, USA; Division of Pediatric Hematology/Oncology, Duke University Medical Center, Durham, NC, USA.
Joseph L WiemelsCenter for Genetic Epidemiology, Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA; Division of Pediatric Hematology/Oncology, Duke University Medical Center, Durham, NC, USA.
Logan G SpectorDivision of Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA; Division of Pediatric Hematology/Oncology, Duke University Medical Center, Durham, NC, USA.
Kyle M WalshPreston Robert Tisch Brain Tumor Center, Department of Neurosurgery, Duke University, Durham, NC, USA; Duke Cancer Institute, Duke University, Durham, NC, USA; Department of Pediatrics, Duke University, Durham, NC, USA; Division of Pediatric Hematology/Oncology, Duke University Medical Center, Durham, NC, USA. Electronic address: Kyle.Walsh@Duke.edu.

Funding

Women's Cancer Research ProgramP30CA014236 · NCI · DUKE UNIVERSITY · PI DONNA NIEDZWIECKI · 1985 to 2026
$174.8M
NCI NIH HHS P30 CA014236
6 · The paper itself

Abstract

backgroundCanine and human osteosarcoma are similar in clinical presentation and tumor genomics. Giant breed dogs experience elevated osteosarcoma incidence, and taller stature remains a consistent risk factor for human osteosarcoma. Whether evolutionarily conserved genes contribute to both human and canine osteosarcoma predisposition merits evaluation.

methodsA multi-center sample of childhood osteosarcoma patients and controls underwent genome-wide genotyping and imputation. Ancestry-adjusted SNP associations were calculated within each dataset using logistic regression, then meta-analyzed across the three datasets, totaling 1091 patients and 3026 controls. Ten regions previously associated with canine osteosarcoma risk were mapped to the human genome, spanning ∼6 Mb. We prioritized association testing of 5985 human SNPs mapping to candidate osteosarcoma risk regions detected in Irish wolfhounds, the largest dog breed studied. Secondary analyses explored 6289 additional human SNPs mapping to candidate osteosarcoma risk regions identified in Rottweilers and greyhounds.

resultsFourteen SNPs were associated with human osteosarcoma risk after adjustment for multiple comparisons, all within a 42 kb region of human Chromosome 7p12.1. The lead variant was rs17454681 (OR=1.25, 95 %CI: 1.12-1.39; P=4.1×10

conclusionsOur comparative oncology analysis identified a novel human osteosarcoma risk allele near GRB10, a growth inhibitor that suppresses activated receptor tyrosine kinases including IGF1R, PDGFRB, and EGFR. Epidemiologists may benefit from leveraging cross-species comparisons to identify haplotypes in highly susceptible but genetically homogenous populations of domesticated animals, then fine-mapping these associations in diverse human populations.

Indexed as

Bone NeoplasmsGenetic Predisposition to DiseaseGenome-Wide Association StudyGRB10 Adaptor ProteinOsteosarcomaPolymorphism, Single NucleotideAdolescentAnimalsCase-Control StudiesChildDog DiseasesDogsFemaleHumansMaleRisk FactorsGRB10 Adaptor ProteinGRB10 protein, humanComparative oncologyGenome-wide association studyGrowth factor receptor bound protein 10Insulin-like growth factor receptorOsteosarcoma

Identifiers

PMID38871555
PMCPMC11402579

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