This variation may be important because epidemiological evidence suggests that elevated levels of serum IGF-I, as absolute concentrations or relative to IGFBP-3, may be associated with an increased risk of breast cancer in premenopausal women (Peyrat et al, 1993; Bruning et al, 1995; Bohlke et al, 1998; Hankinson et al, 1998; Petridou et al, 2000; Toniolo et al, 2000; Kaaks et al, 2002; Krajcik et al, 2002; Muti et al, 2002; Yu et al, 2002; Keinan-Boker et al, 2003). This evidence concerns the gene IGFBP3 and breast cancer.