title: Perinatal factors associated with clinical presentation of osteosarcoma in children and adolescents.
abstract: Osteosarcoma typically develops during puberty with tumors arising at sites of rapid bone growth, suggesting a role for growth-regulating pathways in tumor etiology. Birthweight is one measure of perinatal growth that has been investigated as an osteosarcoma risk factor. Whether birthweight affects clinical features of osteosarcoma remains unexplored.
  
  
  
  Six hundred seventy patients with osteosarcoma, aged 0-19 years, were identified through the California Cancer Registry. We analyzed birth certificate data from the California Department of Public Health vital statistics unit for these patients and 2,860 controls, matched by sex, birth-year, and race/ethnicity. We examined the impact of birthweight on the risk, timing, and clinical presentation of pediatric osteosarcoma including tumor location, size, extension, differentiation, presence of metastasis, and age at onset. Regression models were adjusted for race, sex, gestational age, socioeconomic status, and tumor site.
  
  
  
  Higher birthweight was associated with more advanced tumor stage (P = 0.017), a trend toward greater tumor extension into surrounding tissues (P = 0.083), and with occurrence of tumors in sites other than the long bones of the arms/legs (P = 9.7 × 10-3). Higher birthweight was also associated with an increased likelihood of metastases present at diagnosis (P = 0.047), with each 200 g increase in birthweight associated with a 1.11-fold increase in the odds of having metastatic disease (95% confidence interval: 1.01-1.22).
  
  
  
  The association between higher birthweight and more aggressive osteosarcoma, frequently occurring at sites other than the long bones, suggests that growth pathways active during gestation may play an important role in future osteosarcoma progression, especially at anatomic sites with diminished rates of osteoblastic proliferation.
authors.affiliation: Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, California.|Program in Pediatric Malignancies, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California.
authors.forename: Alyson A
authors.initials: AA
authors.lastname: Endicott
authors.affiliation: Division of Epidemiology, School of Public Health, University of California, Berkeley, California.
authors.forename: Libby M
authors.initials: LM
authors.lastname: Morimoto
authors.affiliation: Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of California, San Francisco, California.
authors.forename: Cassie N
authors.initials: CN
authors.lastname: Kline
authors.affiliation: Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, California.|Department of Epidemiology and Biostatistics, University of California, San Francisco, California.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Wiemels
authors.affiliation: Division of Epidemiology, School of Public Health, University of California, Berkeley, California.
authors.forename: Catherine
authors.initials: C
authors.lastname: Metayer
authors.affiliation: Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, California.|Program in Pediatric Malignancies, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California.|Department of Epidemiology and Biostatistics, University of California, San Francisco, California.
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Walsh
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001724:Birth Weight; D001859:Bone Neoplasms / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology; D002140:California / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009362:Neoplasm Metastasis; D012516:Osteosarcoma / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology; D011247:Pregnancy; D012042:Registries; D012307:Risk Factors
keywords: birthweight; epidemiology; metastasis; osteosarcoma; prenatal growth; puberty