Common genetic variation and risk of osteosarcoma in a multi-ethnic pediatric and adolescent population.

Published online

Journal Article

Osteosarcoma, a malignant primary bone tumor most commonly diagnosed in children and adolescents, has a poorly understood genetic etiology. Genome-wide association studies (GWAS) and candidate-gene analyses have identified putative risk variants in subjects of European ancestry. However, despite higher incidence among African-American and Hispanic children, little is known regarding common heritable variation that contributes to osteosarcoma incidence and clinical presentation across racial/ethnic groups. In a multi-ethnic sample of non-Hispanic white, Hispanic, African-American and Asian/Pacific Islander children (537 cases, 2165 controls), we performed association analyses assessing previously-reported loci for osteosarcoma risk and metastasis, including meta-analysis across racial/ethnic groups. We also assessed a previously described association between genetic predisposition to longer leukocyte telomere length (LTL) and osteosarcoma risk in this independent multi-ethnic dataset. In our sample, we were unable to replicate previously-reported loci for osteosarcoma risk or metastasis detected in GWAS of European-ancestry individuals in either ethnicity-stratified analyses or meta-analysis across ethnic groups. Our analyses did confirm that genetic predisposition to longer LTL is a risk factor for osteosarcoma (ORmeta: 1.22; 95% CI: 1.09-1.36; P = 3.8 × 10-4), and the strongest effect was seen in Hispanic subjects (OR: 1.32; 95% CI: 1.12-1.54, P = 6.2 × 10-4). Our findings shed light on the replicability of osteosarcoma risk loci across ethnicities and motivate further characterization of these genetic factors in diverse clinical cohorts.

Full Text

Duke Authors

Cited Authors

  • Zhang, C; Hansen, HM; Semmes, EC; Gonzalez-Maya, J; Morimoto, L; Wei, Q; Eward, WC; DeWitt, SB; Hurst, JH; Metayer, C; de Smith, AJ; Wiemels, JL; Walsh, KM

Published Date

  • September 13, 2019

Published In

Start / End Page

  • 115070 -

PubMed ID

  • 31525475

Pubmed Central ID

  • 31525475

Electronic International Standard Serial Number (EISSN)

  • 1873-2763

Digital Object Identifier (DOI)

  • 10.1016/j.bone.2019.115070

Language

  • eng

Conference Location

  • United States