title: Genotypes and phenotypes of IGF-I and IGFBP-3 in breast tumors among Chinese women.
abstract: The relationship between IGF genotypes and phenotypes in breast tumors and their associations with breast cancer risk remain to be elucidated. Such information is especially scarce in Chinese women. To evaluate IGF-I and IGFBP-3 genotypes in relation to their phenotypes in local breast tissues and in association with breast cancer risk, we conducted a case-control study among Chinese women. The study recruited 403 breast cancer patients and 403 age-matched controls. Four single nucleotide polymorphisms (SNP) in the IGF-I gene (rs1520220, rs2946834, rs2195239, and rs7965399) and two SNPs of the IGFBP-3 gene (rs2854746 and rs2960436) with known correlations with their phenotypes in the circulation were genotyped using TaqMan assays. Fresh tumor samples from the same patients were analyzed with immunoassays for protein concentrations of IGF-I and IGFBP-3. Associations of breast cancer with these SNPs were examined using unconditional logistic regression. Correlations between IGF genotypes and phenotypes were determined with Wilcoxon rank-sum test. Of the six selected SNPs, only one IGF-I SNP (rs7965399) was associated with breast cancer risk in a recessive model (OR = 1.86; 95% CI: 1.04-3.32), and the association was more evident in patients who had menopause under age 50 or ER negative tumors. No associations were found between breast cancer and other three IGF-I and two IGFBP-3 SNPs. Patients with variant IGF-I or wild IGFBP-3 genotypes had higher peptide levels of IGF-I compared to those with wild IGF-I or variant IGFBP-3 genotypes. The selected IGF-I and IGFBP-3 SNPs did not show any strong evidence for being associated with breast cancer risk, but the genotypes were correlated with IGF-I phenotypes in tumor samples, suggesting possible influences of these SNPs on IGF-I activity in local tissues.
authors.affiliation: Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Huan Hu Xi Rd, He Xi District, Tianjin, 300060, People's Republic of China. qianbiyun@yahoo.com.cn
authors.forename: Biyun
authors.initials: B
authors.lastname: Qian
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.forename: Herbert
authors.initials: H
authors.lastname: Yu
authors.forename: Kexin
authors.initials: K
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D016022:Case-Control Studies; D002681:China; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics* / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I