Breast Cancer Risk in Relation to Serum IGF-I, IGFBP-3 and their Genetic Determinants: A Study Within the European Prospective Investigation into Cancer (EPIC)

摘要

Purpose and scope: we are conducting a large case-control study, nested within a prospective cohort, to estimate relative risks of breast cancer by levels of IGF-I and IGFBP-3, and to examine associations of IGF-I levels and cancer risk with polymorphic variations in a series of 15 candidate genes known to be implicated in the regulation of IGF-I synthesis. Progress report: In this first year of the project, cases and matched control subjects have been identified, their blood samples (serum and buffy coats) were retrieved from a large biorepository, DNA was extracted from buffy coats, and serum IGF-I and IH GFBP-3 were measured. A comprehensive catalogue of single nucleotide polymorphisms (SNPs) in 15 candidate genes was made, by searching databases and by denaturing high-performance chromatography (DHPLC) in our laboratories. Seventy-eight of these SNPs were typed in a cross-sectional sample of subjects, to describe allele and haplotype frequencies. Preliminary statistical analyses, relating the polymorphisms to levels of IGF-I, indicated a subset of 27 polymorphisms that are to be typed with greatest priority in our full study, of 1050 breast cancer cases and 2100 controls. Major findings: First reportable findings are the complete catalogue of SNPs in our list of candidate genes.