Inflammatory Markers in Circulation and Ovarian Cancer Risk

循环中的炎症标志物与卵巢癌风险

• 批准号: 7533037
• 负责人: Alan A. Arslan
• 金额: $ 19.07万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-20 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7533037
• 关键词: Address; Anti-Inflammatory Agents; Anti-inflammatory; Biological; Blood Circulation; Blood specimen; C-reactive protein; Cancer Etiology; Cause of Death; Chronic; Class; Cohort Studies; Condition; DNA; Detection; Development; Diagnostic; Diet; Disease; Early Diagnosis; Epithelial; Epithelial ovarian cancer; General Population; Growth; Health; High Risk Woman; Hormones; Host Defense Mechanism; Individual; Inflammation; Inflammatory; Inflammatory Response; Interleukin-10; Interleukin-12; Interleukin-4; Invasive; Lactation; Leptin; Malignant Female Reproductive System Neoplasm; Malignant Neoplasms; Malignant neoplasm of ovary; Nerve Growth Factor 1; Nerve Growth Factor Pathway; Nested Case-Control Study; New York; Oral Contraceptives; Ovarian; Ovulation; Pathogenesis; Pelvic Inflammatory Disease; Pharmaceutical Preparations; Plasma; Play; Pregnancy; Prevention strategy; Process; Production; Prospective Studies; Public Health; Range; Rare Diseases; Rate; Reactive Oxygen Species; Reproducibility; Research; Risk; Risk Factors; Risk Marker; Role; Sampling; Screening procedure; Serum; Serum Markers; Specificity; Specimen; Suggestion; Sweden; Testing; Universities; Visit; Woman; Women' s Health; adipokines; anakinra; angiogenesis; base; cancer risk; carcinogenesis; cohort; cytokine; endometriosis; follow-up; innovation; member; novel; novel strategies; prospective; repository; resistin; tool

DESCRIPTION (provided by applicant): Ovarian epithelial cancer is the leading cause of death from cancers of female reproductive tract, yet the pathogenesis of the disease is still poorly understood. A growing body of epidemiological evidence suggests that ovarian carcinogenesis may be related to risk factors causing chronic epithelial inflammation. Chronic inflammation has been hypothesized to be involved in cancer development because it promotes growth, invasion, angiogenesis, reactive oxygen species production and suppression of host-defense mechanisms. Several risk factors implicated in ovarian cancer development such as pelvic inflammatory disease, endometriosis, and incessant ovulation, an inflammation-like process, support the hypothesis that inflammation is important in ovarian cancer etiology. Conversely, factors that suppress ovulation (pregnancy, lactation, and use of oral contraceptives) and possibly use of anti-inflammatory medications are associated with reduced risk. These observations led to the suggestion that inflammatory processes play a significant etiologic role in ovarian cancer. We propose to test the hypothesis that the conditions and risk factors characterized by shift to the pro-inflammatory state may increase the risk of epithelial ovarian cancer and, consequently, that circulating markers of inflammation may be directly associated with risk of epithelial ovarian cancer. lentvly, anti-inflammatory markers, which regulate the pro- inflammatory response, are expected to be inversely associated with epithelial ovarian cancer risk. To address these hypotheses, we propose a case-control study nested within three on- going collaborating prospective cohort studies: 1) the New York University Women's Health Study (NYUWHS); 2) the Northern Sweden Health and Disease Study (NSHDS); and 3) the Italian Hormones and Diet in the Etiology of Cancer (ORDET). The participating cohorts have assembled a large volume of baseline and follow-up information on all study members and have access to a valuable repository of blood specimens from all individuals, including serum and plasma samples. The long-term objective of the current application is to develop a panel of novel circulating markers for identification of women at high-risk for ovarian cancer, who subsequently may benefit from more inesve screening for earlier detection of the disease. PUBLIC HEALTH RELEVANCE: The long-term objective of the current application is to develop a panel of new serum markers for identification of women at high-risk for ovarian cancer, who subsequently may benefit from more invasive screening for earlier detection of the disease. The results of the study could be particularly important for development of new approaches to identify women at risk and may provide additional support for development of novel ovarian cancer preventive strategies using anti-inflammatory medications.

描述（由申请人提供）：卵巢上皮癌是女性生殖道癌症死亡的主要原因，但对该疾病的发病机制仍知之甚少。越来越多的流行病学证据表明，卵巢癌的发生可能与引起慢性上皮炎症的危险因素有关。慢性炎症被假设参与癌症的发展，因为它促进生长，侵袭，血管生成，活性氧产生和抑制宿主防御机制。与卵巢癌发展有关的几个危险因素，如盆腔炎、子宫内膜异位症和持续排卵（一种炎症样过程），支持炎症在卵巢癌病因学中很重要的假设。相反，抑制排卵的因素（怀孕，哺乳和口服避孕药的使用）和可能使用抗炎药物与风险降低有关。这些观察结果提示炎症过程在卵巢癌中起重要的病因作用。我们建议测试的假设条件和危险因素的特点是转移到促炎状态可能会增加上皮性卵巢癌的风险，因此，炎症的循环标志物可能与上皮性卵巢癌的风险直接相关。然而，预期调节促炎反应的抗炎标记物与上皮性卵巢癌风险负相关。为了解决这些假设，我们提出了一个病例对照研究嵌套在三个正在进行的合作前瞻性队列研究：1）纽约大学妇女健康研究（NYUWHS）; 2）北方瑞典健康和疾病研究（NSHDS）;和3）意大利激素和饮食在癌症病因学（ORDET）。参与的队列收集了所有研究成员的大量基线和随访信息，并可访问所有个体的血液标本（包括血清和血浆样本）的宝贵储存库。本申请的长期目标是开发一组新的循环标志物，用于鉴定卵巢癌高风险的妇女，这些妇女随后可以受益于更必要的筛查以更早地检测该疾病。公共卫生相关性：本申请的长期目标是开发一组新的血清标志物，用于识别卵巢癌高危女性，这些女性随后可能受益于更早检测疾病的更具侵入性的筛查。该研究的结果对于开发新的方法来识别处于风险中的女性可能特别重要，并可能为开发使用抗炎药物的新型卵巢癌预防策略提供额外的支持。