Intact and total insulin-like growth factor-binding protein-3 (IGFBP-3) levels in relation to breast cancer risk factors: a cross-sectional study

Caroline Diorio¹^,2^,3^,4 , Jacques Brisson²^,3^,4 , Sylvie Bérubé³^,4 and Michael Pollak⁵

¹McGill University, Breast Cancer Functional Genomics Group and McGill Centre for Bioinformatics, 3775 University Street, Montreal, QC H3A 2B4, Canada

²Université Laval, Département de médecine sociale et préventive, 2180 Chemin Sainte-Foy, Québec, QC G1K 7P4, Canada

³Unité de recherche en santé des populations, Centre hospitalier affilié universitaire de Québec, 1050 Chemin Sainte-Foy, Québec, QC G1S 4L8, Canada

⁴Centre des maladies du sein Deschênes-Fabia, Centre hospitalier affilié universitaire de Québec, 1050 Chemin Sainte-Foy, Québec, QC G1S 4L8, Canada

⁵Cancer Prevention Research Unit, Lady Davis Institute of the Jewish General Hospital and McGill University, Departments of Medicine and Oncology, 3755 Cote Ste-Catherine Road, Montreal, QC H3T 1E2, Canada

author email corresponding author email

Breast Cancer Research 2008, 10:R42doi:10.1186/bcr2093


Published:	9 May 2008

Abstract

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 (r_s) 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 (r_s= -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 (r_s= 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.