rs2854746

This nested case-control study (5,253 cases, 4,963 controls) examined 16 SNPs in IGF pathway genes and their associations with prostate cancer risk, testing gene-environment interactions with dietary protein intake. Although the 16 SNPs were significantly associated with circulating IGF-1 or IGFBP-3 levels as expected, none were significantly associated with prostate cancer risk, and the SNP-protein interactions did not substantially differ by protein intake after multiple testing correction.

This study analyzed 521 SNPs in 18 insulin and IGF pathway genes among 1,439 subjects from two chemoprevention trials to identify genetic interactions associated with metachronous colorectal neoplasia. Classification and regression tree (CART) analysis identified gene-by-gene interactions: carriers of the A allele at rs7166348 (IGF1R) with AA genotype at rs1823023 (PIK3R1) had the highest probability of adenoma (71.8%, OR 3.7; 95%CI 2.2-6.5), while those with A at rs7166348, G at rs1823023, and AA at rs10426094 (INSR) had the lowest risk (14.3%, OR 0.22; 95%CI 0.07-0.66). Multifactor dimensionality reduction identified a three-way interaction (rs7166348, rs12609995, rs2715425) with OR 2.12 (95%CI 1.70-2.65) for metachronous neoplasia.

This case-control study examined genetic variants in IGF-I, IGFBP-1, and IGFBP-3 genes in relation to proliferative benign breast disease (BBD) in 359 cases and 359 controls from the Nurses' Health Study II. Higher circulating IGFBP-3 levels were significantly associated with increased BBD risk (OR 1.70, p-trend = 0.03), while minor alleles of IGFBP-3 SNPs rs3110697 and rs2132570 were associated with significantly lower BBD risk (OR 0.6 and 0.2, p-trend = 0.02). Three other IGFBP-3 SNPs (rs2854744, rs2960436, rs2854746) were strongly associated with circulating IGFBP-3 levels.

This study investigated the association between common genetic variation in IGF1, IGFBP1, and IGFBP3 genes and mammographic density in 819 women from the Multiethnic Cohort. Only weak evidence was found for associations: rs35767 (IGF1, p=0.03) was associated with 3.2% lower mammographic density, rs35539615 (IGFBP1, p=0.05) with higher density, and rs2453839 (IGFBP3, p=0.01) with lower density. Ethnicity significantly modified the associations for IGFBP3 variants.

Family-based association study identifying altered transmission of SNPs in HOX gene clusters (HOXA, HOXD) and IGFBP3 as potential risk factors for clubfoot (talipes equinovarus), a common congenital limb defect. Key findings include significant associations with rs3801776 in HOXA (p=0.004 discovery, p=0.028 validation), rs13223993 in IGFBP3 (p=0.003), and strong gene-gene interactions between HOX and apoptotic pathway genes (CASP3, CASP10, Bid, Apaf1), suggesting HOX and apoptotic perturbations affect limb and muscle development.