Abstract 5748: Height, birth-weight, and osteosarcoma risk in a large meta-analysis
Authors: Mirabello Lisa , Pfeiffer Ruth , Murphy Gwen , Daw Najat , Patino-Garcia Ana , Troisi Rebecca , Hoover Robert N. , Douglass Chester , Schuz Joachim , Craft Alan W. , Savage Sharon A. 
Published: February 2011

Abstract
Osteosarcoma (OS) is the most commonly diagnosed primary malignancy of bone. Its primary incidence peak occurs in adolescents and young adults, suggesting that perinatal factors and/or pubertal growth may have a role in etiology. In young patients, OS occurs most frequently at sites of rapid bone growth, the peak incidence occurs earlier in females than males, and males have a higher incidence. Several studies have investigated the relationship between height and birth-weight and OS, but the data are conflicting, therefore, we conducted a meta-analysis of the association of height and birth-weight with OS risk.
We identified 18 studies of OS that included height and/or birth weight. Due to heterogeneity in study findings, the published results of all could not be directly combined. The individual patient data from 6 published studies were obtained from the primary investigators, and 2 unpublished case datasets, resulting in 1067 OS cases with height data, and 434 OS cases with birth-weight data. Since many studies only collected only case information, a control population was created based on the 2000 US National Center for Health Statistics Growth Charts; for each case, 1000 controls were simulated matched on age and gender for height analyses, and matched on gender for birth-weight analyses. Unconditional logistic regression models were used to estimate odds ratios (ORs) for the association between height at diagnosis or birth-weight and risk of OS for each individual study, adjusting for potential confounders. Birth-weight categories were defined based on the lowest 10% and highest 10% of the control distribution. Study specific ORs were combined using random-effects models.
Compared to those of average birth-weight (2665-4045g), patients with low birth-weight (≤2664g) or with high birth-weight (≥4046g) had no significant increased risk of OS [OR 1.09, 95% confidence intervals (CI) 0.78-1.53, and OR 1.41, 95% CI 0.93-2.13, respectively]. By gender, females with high birth-weight had an increased risk of OS (OR 1.49, 95% CI 1.00-2.22); there were no significant associations in males. Patients who were taller (51st to 89th percentile of height for age and gender) than average (≤50th percentile of height) and very tall (≥90th percentile) had a statistically significant increased risk of OS (OR 1.40, 95% CI 1.13-1.73, and OR 2.63, 95% CI 1.98-3.49, respectively; Ptrend &lt;0.0001). A significant trend between increasing height and OS risk was observed in both males and females.
This is the largest aggregated dataset to investigate the associations between height and birth-weight with OS. High birth-weight was associated with increased risk of OS in females, although overall the results did not reach statistical significance. A taller-than-average stature for a person's age and gender significantly increased the risk of OS. This suggests that rapid and/or sustained bone growth during puberty, and possibly in utero, contributes to OS etiology.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5748.