Genetic polymorphisms in the IGFBP3 gene: association with breast cancer risk and blood IGFBP-3 protein levels among Chinese women.

Ren Z, Cai Q, Shu XO, Cai H, Li C, Yu H, Gao YT, Zheng W
Cancer Epidemiol Biomarkers Prev. 2004 13 (8): 1290-5

PMID: 15298948

Cumulative evidence suggests that insulin-like growth factors (IGF) play an important role in the etiology of breast cancer. The IGF binding proteins regulate the action of IGFs, and >90% of circulating IGFs are bound to IGFBP-3. We evaluated the associations of five (A-202C, G227C, C3804G, 5606InsA, and C5827T) genetic polymorphisms in the IGFBP3 gene with breast cancer risk and the blood IGFBP-3 protein level in a population-based, case-control study conducted among Chinese women in Shanghai. Genomic DNA samples from 1,193 incident breast cancer patients and 1,310 community controls were genotyped for IGFBP3 polymorphisms. Blood IGFBP-3 levels were determined for 390 controls. A 30% to 60% elevated risk of breast cancer was found to be associated with homozygosity for the variant allele in polymorphisms A-202C, G227C, 5606InsA, and C5827T. Carrying the variant allele in C3804G was also associated with an increased risk. About 13.5% of cases and 9.7% of controls had one or more of the above risk genotypes, resulting in odds ratio [OR; 95% confidence interval (95% CI)] of 1.4 (1.0-1.9). The ORs (95% CIs) were 1.3 (1.0-1.8) and 1.7 (1.1-2.5) for women with one to two and three to five risk genotypes, respectively (P for trend < 0.01). Four common haplotypes for the IGFBP3 gene were identified. Compared with the haplotype containing only the wild-type allele in the five loci, the haplotype with the variant allele in all sites was associated with an elevated risk of breast cancer (OR 1.4, 95% CI 1.0-1.9), particularly among younger women (OR 2.3, 95% CI 1.3-3.9). With the exception of C3804G, in which no homozygote was identified, the level of circulating IGFBP-3 was reduced in a dose-response manner with an increasing number of variant alleles in each of the other four polymorphic sites (P for trend < 0.05). These results indicated that IGFBP3 polymorphisms may be associated with the level of blood IGFBP-3 protein and an increased risk of breast cancer.

MeSH Terms (22)

Adult Age Distribution Base Sequence Biomarkers, Tumor Breast Neoplasms Case-Control Studies China Confidence Intervals Female Genetic Predisposition to Disease Humans Incidence Insulin-Like Growth Factor Binding Protein 3 Insulin-Like Growth Factor Binding Proteins Middle Aged Molecular Sequence Data Odds Ratio Polymerase Chain Reaction Polymorphism, Genetic Population Surveillance Reference Values Risk Assessment

Connections (2)

This publication is referenced by other Labnodes entities: