Association of Polymorphisms and Haplotypes in the Insulin-Like Growth Factor 1 Receptor (IGF1R) Gene with the Risk of Breast Cancer in Korean Women

The insulin-like growth factor (IGF) signaling pathway plays an important role in cancer biology. The IGF 1 receptor (IGF1R) overexpression has been associated with a number of hematological neoplasias and solid tumors including breast cancer. However, molecular mechanism involving IGF1R in carcinogenic developments is clearly not known. We investigated the genetic variations across the IGF1R polymorphism and the risk of breast cancer risk in Korean women. A total of 1418 individuals comprising 1026 breast cancer cases and 392 age-matched controls of Korean were included for the analysis. Genomic DNA was extracted from whole blood and single nucleotide polymorphisms (SNPs) were analyzed on the GoldenGate Assay system by Illumina’s Custom Genetic Analysis service. SNPs were selected for linkage disequilibrium (LD) analysis by Haploview. We genotyped total 51 SNPs in the IGF1R gene and examined for association with breast cancer. All the SNPs investigated were in Hardy-Weinberg equilibrium. These SNPs tested were significantly associated with breast cancer risk, after correction for multiple comparisons by adjusting for age at diagnosis, BMI, age at menarche, and age at first parturition. Among 51 IGF1R SNPs, five intron located SNPs (rs8032477, rs7175052, rs12439557, rs11635251 and rs12916884) with homozygous genotype (variant genotype) were associated with decreased risk of breast cancer. Fisher’s combined p-value for the five SNPs was 0.00032. Three intron located SNPs with heterozygous genotypes also had decreased risk of breast cancer. 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 case-control study demonstrates statistically significant associations between breast cancer risk and polymorphisms in IGF1R gene.