PILOT EVALUATION OF THE ROLE OF POLYMORPHISMS OF ANGIOGENESIS GENES IN BREAST

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 血管生成在许多生理和病理过程中是重要的。 肿瘤的生长和扩散依赖于血管生成。 肿瘤血管生成增加的几个替代标志物已被证明与不良临床结局相关。 虽然已经对肿瘤本身中体细胞突变的重要性进行了广泛的研究，但在了解生殖系多态性在癌症治疗的发生和反应中的作用方面却做得很少。 已知几个候选基因在该途径中起作用，其在性质上主要是促血管生成或抗血管生成的。 已知这些基因中的几个中的生殖系多态性影响表达，并且与多种恶性肿瘤的发病机制和严重程度有关。 生殖系多态性在血管生成途径中的具体作用尚未系统地研究。 我们使用以下标准来选择用于当前项目研究的基因：1）该基因是有坚实科学基础支持其参与血管生成过程的途径的一部分; 2）该基因具有已建立的、记录良好的多态性; 3）该多态性的频率足够高，使得其在人群水平上对癌症风险的影响将是有意义的; 4）该基因是一种具有遗传学基础的基因。和4）多态性已显示以生物学相关的方式改变基因的功能。 本研究将评估参与血管生成的几个基因多态性在乳腺癌发病机制中的作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Angiogenesis is important in a number of physiologic and pathologic processes. Tumor growth and dissemination depend on angiogenesis. Several surrogate markers of increased tumor angiogenesis have demonstrated an association with poor clinical outcomes. While there has been extensive study of the importance of somatic mutations within the tumor itself, a paucity of work has been done to understand the role of germline polymorphisms in the genesis of and response to cancer therapies. Several candidate genes are known to play a role in this pathway which are predominantly pro-angiogenic or anti-angiogenic in nature. Germline polymorphisms in several of these genes are known to influence expression and have been implicated in the pathogenesis and severity of a variety of malignancies. A specific role for germline polymorphisms within the angiogenesis pathway has not been systematically explored. We used the following criteria to select genes for study in the current project: 1) The gene is part of a pathway for which there is a solid scientific basis to support its involvement in the process of angiogenesis; 2) the gene has an established, well-documented polymorphism; 3) the frequency of the polymorphism is high enough so that its impact on cancer risk at a population level will be meaningful; and 4) the polymorphism has been shown to alter the function of the gene in a biologically relevant manner. This study will evaluate the role of polymorphisms in several genes involved in angiogenesis in the pathogenesis of breast cancer.