Inflammation and gynecologic cancer: the role of prostaglandins in ovarian cancer

项目摘要/摘要 我的最终目标是成为癌症流行病学领域的领导者，进行创新和 妇科癌症病因和预防的高影响力研究。卵巢癌是最致命的 妇科恶性肿瘤；尽管治疗取得了进步，但五年存活率只有44%。我的首要目标是 论文研究旨在通过了解炎症和癌症的作用来改善卵巢癌的预防 卵巢肿瘤发展中的免疫，特别是前列腺素。我的研究将有助于 来自护士健康研究的纵向问卷、生物标记物和组织数据 诊断前前列腺素水平和成人非甾体抗炎药的长期使用模式与糖尿病风险相关 卵巢癌。首先，我将确定诊断前尿前列腺素代谢物PGE-M的水平 与卵巢癌的风险有关。其次，使用生命周期方法，我将评估 考虑到绝经前和绝经后非甾体抗炎药的使用与卵巢癌风险的关系 使用的时间、频率和持续时间。第三，由于卵巢癌是一种高度异质性的疾病，我的 拟议中的研究将确定非甾体抗炎药的使用与卵巢癌风险之间的关系 根据肿瘤侵袭性或肿瘤相关巨噬细胞密度的不同而不同，后者由 前列腺素。该项目的结果将阐明暴露于前列腺素是否会影响卵巢的风险。 癌症，并将提供有关使用非类固醇抗炎药的时间、频率和持续时间的信息，最有可能 做好化学预防。作为一名博士后研究员，我将利用我的博士前培训来分析复杂的 流行病学暴露数据、卵巢肿瘤病理学和生物标记物研究，同时扩大我的研究 包括新陈代谢和基因表达数据的分析。这次培训将使我更好地识别 癌症病因学中的新生物标志物和途径。此外，我将扩大我的研究重点，包括 子宫内膜癌的病因学。有了这些额外的专业知识、不断增长的协作者网络和培训 在撰写拨款的过程中，我将做好充分的准备，开发一个创新的、多学科的癌症研究项目。 流行病学。

PROJECT SUMMARY/ABSTRACT My ultimate goal is to become a leader in the field of cancer epidemiology who conducts innovative and high-impact research on the etiology and prevention of gynecologic cancers. Ovarian cancer is the most fatal gynecologic malignancy; despite advances in treatment, five-year survival is only 44%. The primary goal of my dissertation research is to improve ovarian cancer prevention by understanding the role of inflammation and immunity in ovarian tumor development, with a specific focus on prostaglandins. My research will leverage longitudinal questionnaire, biomarker, and tissue data from the Nurses’ Health Studies to determine how prediagnostic prostaglandin levels and long-term patterns of adult NSAID use are associated with risk of ovarian cancer. First, I will determine whether prediagnostic levels of urinary prostaglandin metabolite PGE-M are associated with risk of ovarian cancer. Second, using a lifecourse approach, I will evaluate the relationships of premenopausal and postmenopausal NSAID use with risk of ovarian cancer, considering timing, frequency, and duration of use. Third, since ovarian cancer is a highly heterogeneous disease, my proposed research will determine whether the association between NSAID use and risk of ovarian cancer differs by tumor aggressiveness or by density of tumor-associated macrophages, which are stimulated by prostaglandins. The results of this project will clarify if exposure to prostaglandins influences risk of ovarian cancer, and will provide information on the timing, frequency and duration of NSAID use that is most likely to be chemopreventive. As a postdoctoral fellow I will leverage my predoctoral training in the analysis of complex epidemiologic exposure data, ovarian tumor pathology, and biomarker research, while expanding my research to include the analysis of metabolomic and gene expression data. This training will allow me to better identify novel biomarkers and pathways in cancer etiology. Further, I will broaden my research focus to include the etiology of endometrial cancer. With this additional expertise, a growing network of collaborators, and training in grant writing, I will be well prepared to develop an innovative, multidisciplinary research program in cancer epidemiology.