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.
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