Abstract The insulin-like growth factor (IGF) signaling axis plays an important role in cancer biology. The insulin-like growth factor 1 receptor (IGF1R) is a tyrosine kinase growth factor receptor that plays important roles in numerous cellular functions and signal transduction pathways. IGF1R may also play a role in the initiation and progression of breast cancer. However, studies of common variation in the IGF1R gene, involved in steroid hormone and IGF-1 metabolism, have yet to provide convincing evidence that such variants predict breast cancer risk. We genotyped 384 tagging single nucleotide polymorphisms (SNPs) in 1026 cases of breast cancer and 392 age-matched control in a population of Korean women. Of the 384 SNPs, fifty one SNPs in the IGF1R gene were examined for association with breast cancer in the study. All the SNPs investigated were in Hardy-Weinberg equilibrium. These SNPs tested were significantly associated with breast cancer risk, after correction for multiple comparisons stratified by adjusting for age at diagnosis, BMI, age at menarche, and age at first parturition. Among 51 IGF1R SNPs, three intron located SNPs (rs8032477, rs11635251, and rs12916884) with homozygous genotype (variant genotype) had increased risk of breast cancer (OR(CI 95%): 0.66(0.44-0.99), 0.54(0.37-0.80), and 0.59(0.37-0.94)). Seven of the 51 IGF1R SNPs were in LD and in one haplotype block, and were likely to be associated with breast cancer risk. Overall, this comprehensive case-control study found statistically significant associations between breast cancer risk and polymorphisms in IGF1R gene. Taking the status of the IGF1R polymorphism into consideration, our results may help in improving the ability to develop effective treatment modalities for those conditions in which IGF1R is involved. To the best of our knowledge, this study is the first to demonstrate the association between IGF1R polymorphisms with the risk of breast cancer.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2610. doi:1538-7445.AM2012-2610