rs2471551

This case-cohort study of 704 postmenopausal women examined 33 SNPs in IGF-I, insulin resistance, and related signaling pathway genes. Six SNPs in INS, IGF-I, and IGFBP3 genes and 11 SNPs in IRS1 and AKT1/2 genes were associated with colorectal cancer risk, with associations differing by obesity status, physical activity, and exogenous estrogen use. Approximately 30-50% of the SNP-cancer association was mediated or influenced by IGF-I/IR traits, suggesting gene-lifestyle interactions affect postmenopausal CRC risk.

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.

Case-control study of 2,774 prostate cancer cases and 1,736 controls examining genetic variation in IGFBP1, IGFBP3, and IGFALS genes in relation to prostate cancer incidence and survival. The rs2854744 variant in IGFBP3 was associated with elevated total IGFBP3 plasma levels (P=9×10⁻⁸), and elevated intact IGFBP3 was associated with increased risk of prostate cancer-specific death (P=6×10⁻¹⁴ unadjusted, P=0.0004 adjusted). No clear associations were found between genetic variants and prostate cancer incidence or overall survival.