Inflammation and Ovarian Cancer

炎症和卵巢癌

• 批准号: 6897459
• 负责人: Roberta B. Ness
• 金额: $ 56.64万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-12 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6897459
• 关键词: Chlamydiaceae; blood chemistry; cancer risk; clinical research; cytokine; enzyme linked immunosorbent assay; female; gene environment interaction; genetic susceptibility; growth factor; heat shock proteins; human subject; inflammation; interview; neoplasm /cancer epidemiology; nonsteroidal antiinflammatory agent; ovary neoplasms; polymerase chain reaction; women' s health

DESCRIPTION (provided by applicant): The cause of ovarian cancer is unclear. We have suggested that inflammation may be involved. Ovulation, endometriosis, and talc use all promote inflammation, and all increase the risk of ovarian cancer; tubal ligation and hysterectomy prevent the ovaries from being exposed to inflammants, and reduce risk. Furthermore, inflammation entails DNA damage and repair, oxidative stress, and elevations in prostaglandins and cytokines, all of which may be mutagenic. Building on our track record of success with conducting ovarian cancer case-control studies, we propose a population-based study to examine the role of inflammation in the risk for ovarian cancer. We will enroll 900 women with incident ovarian cancer (cases) from hospitals in Western Pennsylvania, Northern Ohio, and Western New York. One thousand eight hundred controls, ascertained via random digit dialing, will be frequency matched to cases on age, race, and residence. Using in-person standardized interviews and blood draws, we propose to: 1) evaluate whether non-steroidal anti-inflammatory drugs (NSAIDs) protect against ovarian cancer; 2) compare in cases and controls allelic variants in inflammatory and antinflammatory cytokines and growth factors including IL-1, TNF-a, IL-10, IGF-1 and TGF-b; 3) evaluate whether markers of past PID, i.e. higher antibody titers to chlamydia and its related heat shock protein (HSP)-60, relate to ovarian cancer; 4) in a secondary aim, explore whether allelic variants in the NSAID metabolizing enzymes CYP2C9 and UGT1A6 interact with NSAID use to reduce the risk of ovarian cancer. Exploring the relationships among inflammatory predisposition, inflammatory exposures, anti-inflammatory medications, and ovarian cancer represents a novel avenue of research. In particular, NSAID use may prove to be a potentially important chemopreventative for this often-fatal disease.

描述（由申请人提供）：卵巢癌的病因尚不清楚。我们认为可能涉及炎症。排卵、子宫内膜异位症和滑石粉的使用都会促进炎症，并增加患卵巢癌的风险；输卵管结扎和子宫切除术可防止卵巢暴露于炎症，并降低风险。此外，炎症会导致 DNA 损伤和修复、氧化应激以及前列腺素和细胞因子的升高，所有这些都可能具有诱变性。基于我们进行卵巢癌病例对照研究的成功记录，我们提出了一项基于人群的研究，以检查炎症在卵巢癌风险中的作用。我们将从宾夕法尼亚州西部、俄亥俄州北部和纽约州西部的医院招募 900 名患有卵巢癌（病例）的女性。通过随机数字拨号确定的一千八百个对照将与年龄、种族和居住地的案例进行频率匹配。通过面对面的标准化访谈和抽血，我们建议：1）评估非甾体抗炎药（NSAID）是否可以预防卵巢癌； 2) 比较病例和对照炎症和抗炎细胞因子和生长因子（包括 IL-1、TNF-a、IL-10、IGF-1 和 TGF-b）的等位基因变异； 3) 评估既往PID标志物，即针对衣原体及其相关热休克蛋白（HSP）-60的较高抗体滴度，是否与卵巢癌相关； 4) 第二个目标是探索 NSAID 代谢酶 CYP2C9 和 UGT1A6 中的等位基因变异是否与 NSAID 使用相互作用以降低卵巢癌的风险。探索炎症倾向、炎症暴露、抗炎药物和卵巢癌之间的关系代表了一种新的研究途径。特别是，非甾体抗炎药的使用可能被证明是这种致命疾病的潜在重要化学预防方法。