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

项目总结/摘要 我的最终目标是成为癌症流行病学领域的领导者， 对妇科癌症的病因学和预防进行高影响力的研究。卵巢癌最致命 妇科恶性肿瘤;尽管治疗进展，五年生存率仅为44%。我的主要目标是 论文研究是通过了解炎症的作用来改善卵巢癌的预防， 卵巢肿瘤发展中的免疫力，特别关注前列腺素。我的研究会利用 纵向问卷调查，生物标志物，和组织数据从护士的健康研究，以确定如何 诊断前前列腺素水平和成人NSAID使用的长期模式与以下风险相关： 卵巢癌首先，我将确定尿前列腺素代谢物PGE-M的诊断前水平是否 与卵巢癌的风险有关。其次，使用生命过程方法，我将评估 绝经前和绝经后使用NSAID与卵巢癌风险的关系，考虑到 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， 拟议中的研究将确定NSAID的使用与卵巢癌风险之间是否存在关联， 不同的肿瘤侵袭性或密度的肿瘤相关的巨噬细胞，这是刺激 兰丁该项目的结果将澄清，如果暴露于芦荟素影响卵巢癌的风险， 癌症，并将提供关于NSAID使用的时间，频率和持续时间的信息， 化学预防。作为一名博士后研究员，我将利用我的博士前训练在复杂的分析， 流行病学暴露数据，卵巢肿瘤病理学和生物标志物研究，同时扩大我的研究 包括代谢组学和基因表达数据的分析。这次训练能让我更好地识别 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。有了这些额外的专业知识、不断增长的合作者网络和培训， 在撰写资助申请时，我将为发展一个创新的、多学科的癌症研究项目做好充分的准备 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.