IGF-1Axis and Insulin Resistance in PCPT

描述（由申请人提供）：最近的实验室和流行病学研究提供了胰岛素样生长因子参与前列腺癌发生的证据。几项前瞻性人群研究表明，igf - 1水平升高和胰岛素抵抗是继发前列腺癌的新危险因素，在前列腺癌动物模型中也得到了与这一结论一致的结果。然而，重要的知识差距仍然存在，本应用程序寻求在前列腺癌预防试验提供的独特机会的背景下解决这些问题。研究将进行：(1)测试与IGF生理和/或胰岛素抵抗和/或相关基因多态性相关的血清分析物的基线血清浓度是否与前列腺癌的风险相关，特别是与高级肿瘤的风险相关；(2)调查非那雄胺是否影响这些血清分析物；(3)确定这些血清分析物的基线水平与非那雄胺对前列腺癌风险的影响之间是否存在相互作用。(3)研究这些分析物的浓度是否与细胞凋亡率有关

DESCRIPTION (provided by applicant): Recent laboratory and epidemiologic research has provided evidence that insulin-like growth factors are involved in prostate carcinogenesis. Several prospective population studies suggest that elevated levels of IGF-I and insulin resistance represent novel risk factors for subsequent prostate cancer, and results consistent with this conclusion have been obtained in animal models of prostate carcinogenesis. However, important gaps in knowledge remain, and this application seeks to address these in the context of the unique opportunities provided by the Prostate Cancer Prevention Trial. Research will be undertaken to (1) test whether baseline serum concentrations of serum analytes related to IGF physiology and/or insulin resistance and/or related genetic polymorphisms are associated with risk of prostate cancer in general or high-grade tumors in particular, (2) investigate whether finasteride affects these serum analytes, (3) determine if there are interactions between baseline levels of these serum analytes and the effect of finasteride on prostate cancer risk, and (3) investigate whether concentrations of these analytes are related to apoptosis rate or proliferation rate of at-risk normal prostate cells and/or neoplastic prostate cells. In addition, it will be possible to examine jointly the effects of obesity and IGF levels on risk, and to address the hypothesis that certain dietary risk factors or protective factors for prostate cancer act through mechanisms that involve IGF physiology and/or insulin resistance. The proposed studies involve laboratory measurements to be performed on the extensive serum and tissue banks assembled for PCPT participants, and analysis of these data in conjunction with the PCPT outcome data. The proposed research will provide new basic science information related to prostate carcinogenesis, and also may (1) be relevant to definition of subgroups of men for whom finasteride is particularly valuable as a chemoprevention strategy, (2) aid in defining novel, potentially modifiable risk factors for prostate cancer. The revised Project addresses all reviewer concerns, including that for new preliminary data supporting the tissue IGF signaling studies in collaboration with Core C.