Polymorphisms in the IGF-1 and IGFBP 3 promoter and the risk of breast cancer.

Binding of IGF-1 to the type I IGF receptor starts a signalling cascade that plays an important role in regulating cell proliferation, differentiation and apoptosis. The interaction between the IGF-1 and its receptor is mainly regulated by a binding protein, IGFBP 3. We studied a CA repeat polymorphism 969 bp upstream of the transcription start site in the IGF-1 gene and an A-202 C polymorphism in the IGFBP 3 gene and tested their association with breast cancer risk using four case-control series with a total of 787 cases and 900 controls. We did not find any association between the breast cancer risk and the IGF-1 repeat length (19 versus non-19) or the IGFBP 3 A-202 C polymorphism in the postmenopausal breast cancer series or in women diagnosed for breast cancer under the age of 50. In the familial breast cancer series we observed a non-significantly increased odds-ratio (OR) in homozygotes for the non-19 alleles of the IGF-1 gene (OR 1.51, 95% CI 0.96-2.39, p=0.07). Similarly, in the familial breast cancer series we detected an increased frequency of the IGFBP 3 -202 C allele carriers (OR 1.50, 95% CI 1.05--2.14, p=0.03). The association was stronger in individuals homozygous for these alleles (OR 3.76, 95% CI 1.44-v-9.81, p=0.006). Thus, the polymorphisms in the IGF-1 and IGFBP 3 genes associated with an increased risk of breast cancer in familial cases carrying the variant alleles.