Inflamation and the Risk of Endometrial Cancer

描述（由申请人提供）：通过将哈佛大学公共卫生学院的指导研究经验与正式课程相结合，本提案将支持和丰富Akila N. Viswanathan， MD， MPH，作为一名致力于癌症控制和流行病学学术生涯的研究者的发展。这项拟议的研究将利用护士健康研究数据库分析子宫内膜癌的危险因素。分析将集中在了解炎症在子宫内膜癌发展中的作用。在Aim 1中，拟议的研究项目将阐明抗炎药物的作用，包括阿司匹林和非甾体抗炎药物，与子宫内膜癌的风险有关，并将这些结果与非抗炎药物对乙酰氨基酚的结果进行对比。CYP2C9和UGT1A6基因多态性在阿司匹林代谢中的作用及其作用将被进一步研究。由于在之前的流行病学研究中没有分析过消炎药治疗的作用，因此这项研究将提供对这种癌症的潜在病因和生物学的更彻底的了解，并提供有关使用这些药物在剂量和使用时间方面的影响的公共卫生信息。在目标2中，我们将研究炎症增加对子宫内膜癌风险的作用。具体而言，本项目将使用护士健康研究前瞻性队列分析促炎宫内节育器（IUD）的作用。全身性炎症标志物的作用将通过对生物标志物c反应蛋白和白细胞介素-6的巢式病例对照分析进行评估，首次分析这些生物标志物与子宫内膜癌风险的关系。所有的分析都将由维斯瓦纳坦博士进行。她将获得分析前瞻性队列和病例对照研究、问卷调查、生物标志物和遗传多态性的经验。这项研究的结果将为子宫内膜癌的病因提供重要的新信息，并有助于评估未来的人群风险。通过这笔赠款，维斯瓦纳坦博士将获得流行病学博士学位，从而获得必要的培训，成为该领域的真正专家。这一建议将确保她成为一名成熟的独立研究者和妇科癌症流行病学的主要专家。

DESCRIPTION (provided by applicant): Through the integration of a mentored research experience with formal coursework at the Harvard School of Public Health, this proposal will support and enrich the development of Akila N. Viswanathan, MD, MPH, as an investigator committed to an academic career in cancer control and epidemiology. The proposed research will analyze risk factors for endometrial cancer using the Nurses' Health Study database. The analyses will focus on understanding the role of inflammation in the development of endometrial cancer. In Aim 1, the proposed research project will clarify the role of anti-inflammatory medications, including aspirin and non-steroidal anti-inflammatory drugs, in relation to the risk of endometrial cancer and contrast these results to those of acetaminophen, which is not an anti-inflammatory medication. The role of genetic polymorphisms of the enzymes CYP2C9 and UGT1A6 in the metabolism of aspirin in relation to its effect will be studied. Since the role of treatment with anti-inflammatory drugs has not been analyzed in any prior epidemiologic study, this research will provide a more thorough understanding of the underlying etiology and biology of this cancer and provide public health information on the impact of consumption of these agents with regard to dose and duration of use. In Aim 2, we will examine the role of increased inflammation on the risk of endometrial cancer. Specifically, this project will analyze the role of the pro-inflammatory intra-uterine device (IUD) using the Nurses' Health Study prospective cohorts. The role of markers of systemic inflammation will be assessed by a nested case-control analysis of the biomarkers C-reactive protein and interleukin-6, providing the first analysis of these biomarkers in relation to endometrial cancer risk. All analyses will be performed by Dr. Viswanathan. She will acquire experience in analyzing prospective cohort and case-control studies, questionnaires, biomarkers, and genetic polymorphisms. The results of this proposed research will provide important new information about the etiology of endometrial cancer and assist with the assessment of future population risk. Through this grant, Dr. Viswanathan will obtain a doctoral degree in epidemiology, and thereby will have the requisite training to become a true expert in the field. This proposal will ensure that she will become an established independent investigator and a leading expert in gynecologic cancer epidemiology.