rs2854744

A hospital-based case-control study in rural and urban India (1,204 cases; 1,212 controls) examined genetic and lifestyle risk factors for breast cancer. Four SNPs in FGFR2 (rs1219648, rs2420946, rs2981575, rs2981582) showed positive associations with breast cancer (ORs 1.32-1.47). Additional SNPs in obesity and metabolic genes (rs374748 in FBN2, rs2922763 in HNF4G, rs2116830 in KCNMA1, rs11121832 in MTHFR, rs16886165 in MAP3K1, rs11594610 in TCF7L2, rs2274459 in MLN) were associated with increased breast cancer risk. Waist-to-hip ratio ≥0.95 showed strong association (OR 3.78; 95% CI 2.92-4.89), and women living first 20 years in rural areas showed protective effect (OR 0.77).

Case-control study of 803 bladder cancer patients and 803 healthy controls examining 95 SNPs in 17 RGS (Regulator of G-Protein Signaling) pathway genes. Rs10759 in RGS4 showed the strongest association with reduced bladder cancer risk (OR 0.77, P<0.001), and cumulative analysis of 5 significant SNPs yielded OR 4.13 (95% CI 2.14-7.98) for high-risk genotype combinations. Eleven and thirteen SNPs were associated with recurrence and progression in non-muscle invasive bladder cancer (NMIBC); rs2344673 in RGS5 was most significant for death in muscle-invasive bladder cancer (MIBC), with median survival of 13.3 months vs 81.9 months.

This case-control study of 231 bladder urothelial carcinoma (UC) patients and 261 benign controls found that rs9642880[T] and rs798766[T] variants increase bladder-UC risk (OR=1.72, p=0.028 and OR=1.84, p=0.01 respectively), but unlike upper tract UC, these variants are not associated with disease aggressiveness (grade or stage). The findings highlight distinct genetic differences between bladder-UC and upper urinary tract urothelial carcinoma.

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.

A case-control validation study of 1,450 cases and 1,725 controls from Germany, Hungary, Venezuela, and Pakistan investigated the association of rs2854744 in the IGFBP3 gene with urinary bladder cancer risk. The study found no significant association (P = 0.6510 adjusted for age, gender, and smoking; OR = 1.07, 95% CI 0.86-1.34), failing to confirm the previously published association by Safarinejad et al. A meta-analysis including all available case-control series resulted in an OR of 1.00 (P = 0.9562), indicating no effect of the [A] allele.

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 Iranian case-control study examined the association between the IGFBP-3 A-202C polymorphism (rs2854744) and bladder cancer risk in 162 cancer patients and 324 controls. The study found that the AA genotype was protective against bladder cancer (OR=0.48, 95% CI 0.24-0.64, P=0.001) while the AC genotype increased risk (OR=1.76, 95% CI 1.27-2.84, P=0.038). The protective effect of the AA genotype was more pronounced in advanced bladder cancers, with no AA genotype carriers having high-grade tumors.

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.

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.

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.