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

Details

• Alternative Title:
  Bone
• Personal Author:
  Zhang, Chenan ; Hansen, Helen M. ; Semmes, Eleanor C. ; Gonzalez-Maya, Julio ; Morimoto, Libby ; Wei, Qingyi ; Eward, William C. ; DeWitt, Suzanne B. ; Hurst, Jillian H. ; Metayer, Catherine ; de Smith, Adam J. ; Wiemels, Joseph L. ; Walsh, Kyle M.
• Description:
  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 (OR|: 1.22; 95% CI: 1.09-1.36; P = 3.8 × 10|), and the strongest effect was seen in Hispanic subjects (OR: 1.32; 95% CI: 1.12-1.54, P = 6.2 × 10|). 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.
• Subjects:
  Adolescent Child Ethnicity Genetic Predisposition To Disease Genome-Wide Association Study Hispanic Or Latino Humans Osteosarcoma Polymorphism, Single Nucleotide
• Keywords:
  Buprenorphine Genome-wide Association Study Mendelian Randomization Methadone Mortality Naltrexone Polygenic Risk Score Treatment
• Source:
  Bone. 130:115070
• Pubmed ID:
  31525475
• Pubmed Central ID:
  PMC6885126
• Document Type:
  Journal Article
• Funding:
  HHSN261201800032C/CA/NCI NIH HHSUnited States/ ; HHSN261201800009C/CA/NCI NIH HHSUnited States/ ; NU58DP006344/DP/NCCDPHP CDC HHSUnited States/ ; T32 CA151022/CA/NCI NIH HHSUnited States/ ; HHSN261201800015I/CA/NCI NIH HHSUnited States/ ; R01 CA155461/CA/NCI NIH HHSUnited States/ ; R01 CA194189/CA/NCI NIH HHSUnited States/ ; HHSN261201800032I/CA/NCI NIH HHSUnited States/ ; HHSN261201800009I/CA/NCI NIH HHSUnited States/ ; T32 GM007171/GM/NIGMS NIH HHSUnited States/ ; HHSN261201800015C/CA/NCI NIH HHSUnited States/
• Volume:
  130
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:af1c4fd6aca8dcd61e9c4e6718d22a025b7f137cb3d997ed12b230c7fc8b8f4b93c65d68435b645c2ce43992e39efddb67faf172e2b77ed87cc645c5db490caf
• Download URL:
  https://stacks.cdc.gov/view/cdc/149754/cdc_149754_DS1.pdf
• File Type:
  [PDF - 1.20 MB ]