This research trial studies blood samples from patients with osteosarcoma. Studying the genes found in samples of blood from patients with osteosarcoma may help doctors identify biomarkers related to the disease.
PRIMARY OBJECTIVE: I. Conduct a large-scale candidate gene association study in osteosarcoma (OS) using cases from the national Children's Oncology Group (COG) OS biology study (P9851 and successor study AOST06B1). SECONDARY OBJECTIVES: I. Conduct a genome-wide association study (GWAS) of OS. II. Fine-map genomic regions associated with OS to identify putative functional loci. III. Conduct whole-exome sequencing of germline OS deoxyribonucleic acid (DNA) samples. IV. Investigate the functional implications of promising genetic variants associated with OS. OUTLINE: Blood samples undergo polymorphism analysis of common single-nucleotide polymorphisms and haplotypes to examine genetic variation, gene-gene interactions, and the population structure.
Study Type
OBSERVATIONAL
Enrollment
1,000
Correlative studies
Children's Oncology Group
Arcadia, California, United States
Hardy-Weinberg equilibrium on all SNPs
Determined on all SNPs by chi-square tests.
Time frame: Baseline
SNPs associated with OS
Logistic regression will be used to estimate odds ratios and 95% confidence intervals for the association between each SNP and OS under co-dominant, dominant and recessive genetic models. Stratified analyses will be conducted to examine sex, tumor subtype and outcome differences.
Time frame: Baseline
Gene-gene interactions
Assessed using a multiplicative model. Haplotypes will be constructed using both Bayesian and expectation-maximization algorithms. Differences between cases and controls will be evaluated with HaploStats which uses haplotype posterior probabilities as weights to update the regression coefficients in an iterative manner.
Time frame: Baseline
Survival outcomes
Kaplan-Meier survival curves will be used to determine outcome relative to genotype.
Time frame: Baseline
Whole-exome variant loci
Annotation and filtering of each whole-exome variant locus will be performed using a custom software pipeline. Variants in \>= 2 OS cases will be validated, and then subsequently replicated in additional OS cases (samples previously received for the GWAS from international collaborators). Variants will also be evaluated for presence in known biologically plausible pathways and genes.
Time frame: Baseline
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