The A(-336C) insulin-like growth factor binding protein-3 promoter polymorphism is not a modulator of breast cancer risk in Caucasian women.

Insulin-like growth factors (IGF) play an important role in the proliferation and apoptosis of several cell types and may therefore be associated with the risk of malignant transformation (1). IGF binding protein-3 (IGFBP-3) is the most common binding protein for IGF-I in serum. High levels of IGFBP-3 are associated with reduced IGF-I levels and thereby influence cell proliferation by modulating access of IGFs to the IGF receptors. In healthy women, alcohol consumption was found to suppress IGF-I and IGFBP-3 levels, and the use of oral contraceptives reduced IGF-I levels and increased IGFBP-3 levels (2). There is increasing evidence from prospective cohort as well as case-control studies that increased serum IGF-I levels are associated with an increased breast cancer risk among premenopausal women (3). Serum IGFBP-3 levels have not consistently been found to be related to breast cancer risk. Recently, an A ! C polymorphism in the IGFBP-3 promoter region was identified that is related to circulating IGFBP-3 levels (4). The AA genotype was associated with higher circulating IGFBP-3 levels than the AC or CC genotype in men and in premenopausal women (4, 2). The genotypephenotype correlation was modified by body mass index and height (4). Further, it has been shown in in vitro tests that the A allele has higher promoter activity than the C allele (4).