Genotypes and phenotypes of IGF-I and IGFBP-3 in breast tumors among Chinese women
Genotypes and phenotypes of IGF-I and IGFBP-3 in breast tumors among Chinese women
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DOI：
10.1007/s10549-011-1552-9
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发表时间：
2011-11-01
影响因子：
3.8
通讯作者：
Chen, Kexin
中科院分区：
文献类型：
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作者：
Qian, Biyun;Zheng, Hong;Chen, Kexin
乳腺肿瘤中IGF基因型和表型之间的关系及其与乳腺癌风险的关系仍有待阐明。这样的信息在中国女性中尤其稀缺。为了评估igf - 1和IGFBP-3基因型与其局部乳腺组织表型的关系以及与乳腺癌风险的关系，我们在中国女性中进行了一项病例对照研究。这项研究招募了403名乳腺癌患者和403名年龄匹配的对照组。利用TaqMan方法对igf - 1基因的4个单核苷酸多态性（SNP） （rs1520220、rs2946834、rs2195239和rs7965399）和IGFBP-3基因的2个SNP （rs2854746和rs2960436）进行基因分型。用免疫分析法分析来自同一患者的新鲜肿瘤样本中IGF-I和IGFBP-3的蛋白浓度。使用无条件逻辑回归检查乳腺癌与这些snp的关联。采用Wilcoxon秩和检验确定IGF基因型与表型的相关性。在选择的6个SNP中，只有1个igf - 1 SNP （rs7965399）在隐性模型中与乳腺癌风险相关（OR = 1.86; 95% CI: 1.94 -3.32），并且在50岁以下绝经或ER阴性肿瘤患者中相关性更为明显。乳腺癌与其他三个igf - 1和两个IGFBP-3 snp之间没有关联。变异IGF-I或野生IGFBP-3基因型患者的IGF-I肽水平高于野生IGF-I或变异IGFBP-3基因型患者。所选的IGF-I和IGFBP-3 snp没有显示出与乳腺癌风险相关的任何强有力的证据，但基因型与肿瘤样本中的IGF-I表型相关，这表明这些snp可能影响局部组织中IGF-I的活性。
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.