胰岛素样生长因子及其受体和结合蛋白的基因型和单倍型与血浆代谢水平和乳腺 X 光密度的关系。
Genotypes and haplotypes in the insulin-like growth factors, their receptors and binding proteins in relation to plasma metabolic levels and mammographic density.
机构信息
Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Montebello 0310, Oslo, Norway.
出版信息
BMC Med Genomics. 2010 Mar 19;3:9. doi: 10.1186/1755-8794-3-9.
BACKGROUND
Increased mammographic density is one of the strongest independent risk factors for breast cancer. It is believed that one third of breast cancers are derived from breasts with more than 50% density. Mammographic density is affected by age, BMI, parity, and genetic predisposition. It is also greatly influenced by hormonal and growth factor changes in a woman's life cycle, spanning from puberty through adult to menopause. Genetic variations in genes coding for hormones and growth factors involved in development of the breast are therefore of great interest. The associations between genetic polymorphisms in genes from the IGF pathway on mammographic density and circulating levels of IGF1, its binding protein IGFBP3, and their ratio in postmenopausal women are reported here.
METHODS
Samples from 964 postmenopausal Norwegian women aged 55-71 years were collected as a part of the Tromsø Mammography and Breast Cancer Study. All samples were genotyped for 25 SNPs in IGF1, IGF2, IGF1R, IGF2R, IGFALS and IGFBP3 using Taqman (ABI). The main statistical analyses were conducted with the PROC HAPLOTYPE procedure within SAS/GENETICS (SAS 9.1.3).
RESULTS
The haplotype analysis revealed six haploblocks within the studied genes. Of those, four had significant associations with circulating levels of IGF1 or IGFBP3 and/or mammographic density. One haplotype variant in the IGF1 gene was found to be associated with mammographic density. Within the IGF2 gene one haplotype variant was associated with levels of both IGF1 and IGFBP3. Two haplotype variants in the IGF2R were associated with the level of IGF1. Both variants of the IGFBP3 haplotype were associated with the IGFBP3 level and indicate regulation in cis.
CONCLUSION
Polymorphisms within the IGF1 gene and related genes were associated with plasma levels of IGF1, IGFBP3 and mammographic density in this study of postmenopausal women.
背景
乳腺密度增加是乳腺癌的最强独立危险因素之一。据信，三分之一的乳腺癌源自乳腺密度超过 50%的乳房。乳腺密度受年龄、BMI、生育次数和遗传易感性的影响。它还受到女性生命周期中激素和生长因子变化的极大影响，从青春期到成年期到绝经期。因此，参与乳腺发育的激素和生长因子编码基因中的遗传变异非常重要。报告了 IGF 通路基因中的遗传多态性与绝经后妇女的乳腺密度和循环 IGF1 水平及其结合蛋白 IGFBP3 及其比值之间的关联。
方法
964 名 55-71 岁的绝经后挪威女性的样本作为特罗姆瑟乳腺 X 线摄影和乳腺癌研究的一部分进行收集。使用 Taqman（ABI）对 IGF1、IGF2、IGF1R、IGF2R、IGFALS 和 IGFBP3 中的 25 个 SNP 进行基因分型。主要统计分析使用 SAS/GENETICS（SAS 9.1.3）中的 PROC HAPLOTYPE 过程进行。
结果
单体型分析显示，在所研究的基因中存在六个单体型块。其中，有四个与循环 IGF1 或 IGFBP3 水平和/或乳腺密度有显著关联。IGF1 基因中的一个单体型变体与乳腺密度有关。在 IGF2 基因中，一个单体型变体与 IGF1 和 IGFBP3 的水平都有关。IGF2R 中的两个单体型变体与 IGF1 水平有关。IGFBP3 单体型的两个变体都与 IGFBP3 水平有关，表明在 cis 中存在调节作用。
结论
在这项对绝经后妇女的研究中，IGF1 基因和相关基因中的多态性与 IGF1、IGFBP3 和乳腺密度的血浆水平相关。
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