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利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 血管生成在许多生理和病理过程中都很重要。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记物已经证明与不良的临床结果有关。 虽然已经有广泛的研究表明体细胞突变在肿瘤本身中的重要性，但在了解生殖系多态在癌症治疗的发生和反应中的作用方面做的工作很少。已知有几个候选基因在这一途径中发挥作用，这些基因本质上主要是促血管生成或反血管生成。已知其中几个基因的胚系多态会影响基因的表达，并与多种恶性肿瘤的发病机制和严重程度有关。胚系多态在血管生成途径中的具体作用尚未被系统地探讨。在目前的项目中，我们使用以下标准来选择用于研究的基因：1)该基因是有坚实的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、有充分证据的多态；3)该多态的频率足够高，因此其在人群水平上对癌症风险的影响将是有意义的；以及4)该多态已被证明以一种生物相关的方式改变了该基因的功能。 本研究将评估参与血管生成的几个基因的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.