title: Case-parent analysis of variation in pubertal hormone genes and pediatric osteosarcoma: a Children's Oncology Group (COG) study.
abstract: Osteosarcoma (OS) is a rare malignant bone tumor with an overall incidence rate of 4.6 cases per million children aged 0-19 years in the United States. While the etiology of OS is largely unknown, its distinctive age-incidence pattern suggests that growth and development is crucial in genesis. Prior studies have suggested that variants in genes in the estrogen metabolism (ESTR) and insulin-like growth factor/growth hormone (IGF/GH) pathways are associated with OS. We examined 798 single nucleotide polymorphisms (SNPs) in 42 genes from these pathways in a case-parent study (229 complete triads and 56 dyads) using buccal cell samples. Relative risks (RR) and 95% confidence intervals (CI) associated with transmitting one or two copies of the variant were estimated using log-linear models. After Bonferroni correction, 1 SNP within the ESTR pathway (rs1415270: RR = 0.50 and 8.37 for 1 and 2 vs. 0 copies, respectively; p = 0.010), and two SNPs in the IGF/GH pathway (rs1003737: RR = 0.91 and 0.0001 for 1 and 2 vs. 0 copies, respectively; p <0.0001 and rs2575352: RR = 2.62 and 0.22 for 1 and 2 vs. 0 copies; p < 0.0001) were significantly associated with OS incidence. These results confirm previous findings that variation in the estrogen metabolism and bone growth pathways influence OS risk and further support a biologically and epidemiologically plausible role in OS development.
authors.affiliation: Division of Pediatric Epidemiology and Clinical Research, University of Minnesota Minneapolis MN 55455.
authors.forename: Jessica Rb
authors.initials: JR
authors.lastname: Musselman
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Bergemann
authors.forename: Julie A
authors.initials: JA
authors.lastname: Ross
authors.forename: Charles
authors.initials: C
authors.lastname: Sklar
authors.forename: Kevin At
authors.initials: KA
authors.lastname: Silverstein
authors.forename: Erica K
authors.initials: EK
authors.lastname: Langer
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Savage
authors.forename: Rajaram
authors.initials: R
authors.lastname: Nagarajan
authors.forename: Mark
authors.initials: M
authors.lastname: Krailo
authors.forename: David
authors.initials: D
authors.lastname: Malkin
authors.forename: Logan G
authors.initials: LG
authors.lastname: Spector