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Genetic polymorphisms in the IGFBP3 gene: association with breast cancer risk and blood IGFBP-3 protein levels among Chinese women.
Cancer Epidemiol Biomarkers Prev. 2004 Aug; 13(8):1290-5.CE

Abstract

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.

Authors+Show Affiliations

Department of Medicine, Vanderbilt University, Nashville, TN, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15298948

Citation

Ren, Zefang, et al. "Genetic Polymorphisms in the IGFBP3 Gene: Association With Breast Cancer Risk and Blood IGFBP-3 Protein Levels Among Chinese Women." Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, vol. 13, no. 8, 2004, pp. 1290-5.
Ren Z, Cai Q, Shu XO, et al. Genetic polymorphisms in the IGFBP3 gene: association with breast cancer risk and blood IGFBP-3 protein levels among Chinese women. Cancer Epidemiol Biomarkers Prev. 2004;13(8):1290-5.
Ren, Z., Cai, Q., Shu, X. O., Cai, H., Li, C., Yu, H., Gao, Y. T., & Zheng, W. (2004). Genetic polymorphisms in the IGFBP3 gene: association with breast cancer risk and blood IGFBP-3 protein levels among Chinese women. Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, 13(8), 1290-5.
Ren Z, et al. Genetic Polymorphisms in the IGFBP3 Gene: Association With Breast Cancer Risk and Blood IGFBP-3 Protein Levels Among Chinese Women. Cancer Epidemiol Biomarkers Prev. 2004;13(8):1290-5. PubMed PMID: 15298948.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic polymorphisms in the IGFBP3 gene: association with breast cancer risk and blood IGFBP-3 protein levels among Chinese women. AU - Ren,Zefang, AU - Cai,Qiuyin, AU - Shu,Xiao-Ou, AU - Cai,Hui, AU - Li,Chun, AU - Yu,Herbert, AU - Gao,Yu-Tang, AU - Zheng,Wei, PY - 2004/8/10/pubmed PY - 2004/11/9/medline PY - 2004/8/10/entrez SP - 1290 EP - 5 JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology JO - Cancer Epidemiol Biomarkers Prev VL - 13 IS - 8 N2 - 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. SN - 1055-9965 UR - https://www.unboundmedicine.com/medline/citation/15298948/Genetic_polymorphisms_in_the_IGFBP3_gene:_association_with_breast_cancer_risk_and_blood_IGFBP_3_protein_levels_among_Chinese_women_ DB - PRIME DP - Unbound Medicine ER -