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1: Breast Cancer Res. 2008;10(3):R42. Epub 2008 May 9.
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Intact and total insulin-like growth factor-binding protein-3 (IGFBP-3) levels in relation to breast cancer risk factors: a cross-sectional study.

Diorio C, Brisson J, Bérubé S, Pollak M.

McGill University, Breast Cancer Functional Genomics Group and McGill Centre for Bioinformatics, 3775 University Street, Montreal, QC H3A 2B4, Canada. caroline.diorio@uresp.ulaval.ca.

INTRODUCTION: Levels of insulin-like growth factor (IGF)-I and its main binding protein (IGFBP-3) have been associated with breast cancer risk among premenopausal women. However, associations of IGFBP-3 levels with breast cancer risk have been inconsistent, possibly due to the different predominant forms of circulating IGFBP-3 (intact versus fragmented) that were measured in these studies. Here, we examine the association of breast cancer risk factors with intact and total IGFBP-3 levels. METHODS: This cross-sectional study includes 737 premenopausal women recruited at screening mammography. Plasma intact and total IGFBP-3 and IGF-I levels were measured by enzyme-linked immunosorbent assay methods. Percent and absolute breast density were estimated using a computer-assisted method. The associations were evaluated using generalized linear models and Pearson (r) or Spearman (rs) partial correlation coefficients. RESULTS: Means +/- standard deviations of intact and total IGFBP-3 levels (ng/mL) were 1,044 +/- 234 and 4,806 +/- 910, respectively. Intact and total IGFBP-3 levels were correlated with age and smoking. Levels of intact IGFBP-3 were negatively correlated with waist-to-hip ratio (WHR) (r = -0.128; P = 0.0005), parity (rs = -0.078; P = 0.04), and alcohol intake (r = -0.137; P = 0.0002) and positively correlated with energy intake (r = 0.075; P = 0.04). In contrast, total IGFBP-3 levels were positively correlated with WHR (r = 0.115; P = 0.002), parity (rs = 0.089; P = 0.02), body mass index (BMI) (r = 0.115; P = 0.002), physical activity (r = 0.118; P = 0.002), and IGF-I levels (r = 0.588; P < 0.0001) and negatively correlated with percent or absolute breast density (r = -0.095; P = 0.01 and r = -0.075; P = 0.04, respectively). CONCLUSION: Our data show that associations of some breast cancer risk factors with intact levels of IGFBP-3 are different from those with total (intact and fragmented) IGFBP-3 levels. These findings suggest that different molecular forms of IGFBP-3 may bear different relations to premenopausal breast cancer risk.

Publication Types:
PMID: 18471292 [PubMed - indexed for MEDLINE]

PMCID: PMC2481489