Inflammatory Markers in Circulation and Ovarian Cancer Risk

描述（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，但其发病机制尚不清楚。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。慢性炎症被认为与癌症的发展有关，因为它促进生长、侵袭、血管生成、活性氧的产生和宿主防御机制的抑制。一些与卵巢癌发展相关的危险因素，如盆腔炎、子宫内膜异位症和不间断排卵（一种类似炎症的过程），支持了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、哺乳和使用口服避孕药）和可能使用抗炎药物与降低风险有关。这些观察结果表明，炎症过程在卵巢癌的病因学中起着重要作用。我们建议验证以促炎状态转变为特征的条件和危险因素可能会增加上皮性卵巢癌的风险，因此，循环炎症标志物可能与上皮性卵巢癌的风险直接相关。目前，调节促炎反应的抗炎标志物预计与上皮性卵巢癌风险呈负相关。为了解决这些假设，我们在三个正在进行的合作前瞻性队列研究中提出了一项病例对照研究：1)纽约大学妇女健康研究（NYUWHS）；瑞典北部健康和疾病研究（NSHDS）；3)意大利激素和饮食在癌症病因学中的作用（ORDET）。参与队列收集了所有研究成员的大量基线和随访信息，并可获得所有个体的宝贵血液标本库，包括血清和血浆样本。当前应用的长期目标是开发一组新的循环标志物，用于识别卵巢癌高危妇女，这些妇女随后可能受益于更有效的筛查，以早期发现该疾病。公共卫生相关性：当前应用的长期目标是开发一组新的血清标记物，用于识别卵巢癌高危妇女，这些妇女随后可能受益于更有创性的筛查，以早期发现该疾病。这项研究的结果对于鉴别有风险的女性的新方法的发展尤其重要，并可能为使用抗炎药物的新型卵巢癌预防策略的发展提供额外的支持。

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.