Data from Eighteen Insulin-like Growth Factor Pathway Genes, Circulating Levels of IGF-I and Its Binding Protein, and Risk of Prostate and Breast Cancer

<div>Abstract<p><b>Background:</b> Circulating levels of insulin-like growth factor I (IGF-I) and its main binding protein, IGF binding protein 3 (IGFBP-3), have been associated with risk of several types of cancer. Heritable factors explain up to 60% of the variation in IGF-I and IGFBP-3 in studies of adult twins.</p><p><b>Methods:</b> We systematically examined common genetic variation in 18 genes in the IGF signaling pathway for associations with circulating levels of IGF-I and IGFBP-3. A total of 302 single nucleotide polymorphisms (SNP) were genotyped in >5,500 Caucasian men and 5,500 Caucasian women from the Breast and Prostate Cancer Cohort Consortium.</p><p><b>Results:</b> After adjusting for multiple testing, SNPs in the <i>IGF1</i> and <i>SSTR5</i> genes were significantly associated with circulating IGF-I (<i>P</i> < 2.1 × 10<sup>−4</sup>); SNPs in the <i>IGFBP3</i> and <i>IGFALS</i> genes were significantly associated with circulating IGFBP-3. Multi-SNP models explained <i>R</i><sup>2</sup> = 0.62% of the variation in circulating IGF-I and 3.9% of the variation in circulating IGFBP-3. We saw no significant association between these multi-SNP predictors of circulating IGF-I or IGFBP-3 and risk of prostate or breast cancers.</p><p><b>Conclusion:</b> Common genetic variation in the <i>IGF1</i> and <i>SSTR5</i> genes seems to influence circulating IGF-I levels, and variation in <i>IGFBP3</i> and <i>IGFALS</i> seems to influence circulating IGFBP-3. However, these variants explain only a small percentage of the variation in circulating IGF-I and IGFBP-3 in Caucasian men and women.</p><p><b>Impact:</b> Further studies are needed to explore contributions from other genetic factors such as rare variants in these genes and variation outside of these genes. Cancer Epidemiol Biomarkers Prev; 19(11); 2877–87. ©2010 AACR.</p></div>