Abstract B78: Adiposity and the IGF-axis in girls during pubertal development

Abstract

Abstract Background: Increased childhood adiposity has been associated with decreased breast cancer risk, but the biologic mechanisms underlying this association are not well understood. Pubertal growth is in part driven by the insulin-like growth factor (IGF) system and adult measures of IGF have been associated with breast cancer. We hypothesize that childhood adiposity is associated with the IGF-axis and that levels set in childhood affect later breast cancer risk. We prospectively examine associations between childhood adiposity, as measured by body mass index (BMI)-for-age percentile (BMIPCT), and serum IGF-axis biomarkers (IGF-I, IGF binding protein 1(IGFBP-1), and IGF binding protein 3 (IGFBP-3)) among girls in the Dietary Intervention Study in Children (DISC). Methods: Data are from an ancillary hormone study of 268 of the 301 girls who participated in the DISC. Girls were 8-10 years old at baseline with a median follow-up of 7 years. Data from intervention and control groups were combined and intervention status was included in adjusted analyses. Fasting blood samples (n=563) collected at baseline, years 3, 5 and last visit were available for 219 premenarcheal and 201 postmenarcheal girls. Levels of IGF-I, IGFBP-1, and IGFBP-3 were determined using radioimmunoassays. Weight and height measurements were taken at baseline and subsequent visits by trained interviewers. BMI (weight/height2)–for-age percentiles were determined using the CDC growth chart. To mitigate skewness, biomarkers were log transformed. Adjusted geometric means of IGF biomarkers were calculated by quintiles of baseline BMIPCT. All adjusted analyses included age, age2, treatment group, baseline height, and physical activity. Associations of longitudinal BMIPCT with IGF biomarkers were estimated using multivariable linear mixed-effect models, accounting for repeated BMIPCT and IGF measurements within each girl across follow-up visits. Trend tests were performed on continuous BMIPCT using adjusted mixed-effect models to estimate percentage changes in IGF biomarkers during follow-up. Results: In adjusted analyses, premenarcheal girls in the lowest quintile of baseline BMIPCT had lower geometric mean IGF-I levels than all other quintiles (Q1= 236 ng/mL (95% confidence interval (CI): 211, 264) vs. Q5 mean=271 ng/ml (95% CI: 240, 307)). Girls in the lowest quintile of BMIPCT had higher IGFBP-1 levels that decreased linearly with BMIPCT quintile (Ptrend <0.0001). In continuous analyses, each 10 percentile increment in baseline BMIPCT was associated with a 2.4% increase (95% CI: 0.5%, 4.2%) in IGF-I (Ptrend=0.01) and a 7.2% decrease (95% CI: 4.9%, 9.6%) in IGFBP-1 (Ptrend<0.0001). There was no significant association between IGFBP-3 and BMIPCT. In post-menarcheal girls, each 10 percentile increment in baseline BMIPCT was associated with a 12.0% decrease (95% CI: 8.4 %,15.6%) in IGFBP-1 (Ptrend<0.0001), but no significant association with IGF-I or IGFBP-3. Conclusion: This study suggests that premenarcheal girls in the lowest quintile of BMI-for-age have lower IGF-I levels than in all other quintiles. Results also show increased adiposity, as measured by BMI-for-age, is significantly associated with decreased IGFBP-1 in both pre- and postmenarcheal girls. Further research is needed to confirm these findings, as well as to explore possible associations with breast development and potentially breast cancer risk. Citation Format: Ellen M. Velie, Zhenzhen Zhang, Jean M. Kerver, Joseph C. Gardiner, Clifford J. Rosen, Joanne F. Dorgan. Adiposity and the IGF-axis in girls during pubertal development. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B78.