Ovarian Cancer

在这个项目中，我们建议继续调查潜在的可改变的营养和激素风险 发生卵巢癌的因素。这项工作将使用前瞻性收集的问卷数据，生物学 样本和石蜡包埋的卵巢肿瘤组织，来自护士健康研究(NHS)和 NHSII。尽管关于卵巢癌的病因提出了几种假说，但几乎没有可修改的假说。 生活方式的危险因素已经被确定。我们将研究维生素D可能的预防作用。 卵巢癌，目的是确定最能从干预中受益的亚群。我们 也将评估三个饮食因素：可降低风险的类黄酮；青春期的乳糖和 成年期；以及丙烯酰胺摄入量和红细胞加合物水平，这两者都可能增加风险。我们也 将评估褪黑素和轮班工作在卵巢癌发生中的作用。此外，我们建议 测量循环炎症标志物(CPR、IL-6和TNFa-R2)和与以下各项相关的肿瘤标志物 炎症(例如，统计数据)。我们还首次提出专门关注致命的卵巢癌， 努力找出可能使女性患上快速生长的肿瘤或 易发生转移的腹膜环境。同样，我们计划评估荷尔蒙受体 卵巢肿瘤及其与危险因素的关系，重点是探索卵巢肿瘤的新模型 癌变(生长缓慢的肿瘤与生长迅速的肿瘤)作为流行病学肿瘤分类的一种方法 学习。该项目与项目1和项目2有共同的生物学主题，包括维生素D的作用， 褪黑素和炎症途径，并在方法学问题上与项目4密切互动。它还 与其他项目共享由核心A提供的强大的行政和科学基础设施 (队列随访和数据库维护)、B(癌症和死因确认)、C (生物检疫管理)和D(领导和数据分析)。这些发现应该会加强 了解卵巢癌的病因和进展，为妇女和妇女提供指导 卫生保健提供者为减少这种疾病的痛苦和死亡所做的努力。

In this Project, we propose to continue the investigation of potentially modifiable nutritional and hormonal risk factors for incident ovarian cancer. This work will use prospectively collected questionnaire data, biological samples, and paraffin-embedded ovarian tumor tissue from women in the Nurses' Health Study (NHS) and NHSII. Although several hypotheses regarding ovarian cancer etiology have been proffered, few modifiable lifestyle risk factors have been identified. We will examine the possible preventive role of vitamin D in ovarian cancer, with the goal of identifying subpopulations who could most benefit from intervention. We also will evaluate three dietary factors: flavonoids, which may reduce risk; lactose in adolescence and adulthood; and acrylamide intake and red blood cell adduct levels, both of which may increase risk. We also will evaluate the role of melatonin and shift work in ovarian carcinogenesis. In addition, we propose to measure circulating markers of inflammation (CPR, IL-6, and TNFa-R2) and tumor markers associated with inflammation (e.g., STATs). We also propose for the first time to focus specifically on fatal ovarian cancer, with an effort to identify risk factors that may predispose women to either having fast-growing tumors or a peritoneal environment susceptible to metastasis. In this same vein, we plan to evaluate hormone receptors in ovarian tumors and their relation to risk factors, with an emphasis on exploring a new model of ovarian carcinogenesis (slow-growing tumors vs. fast-growing tumors) as a way to classify tumors in epidemiologic studies. The Project shares common biological themes with Projects 1 and 2, including the role of vitamin D, melatonin, and the inflammation pathway and interacts closely with Project 4 for methodologic issues. It also shares with the other Projects a strong administrative and scientific infrastructure provided by Cores A (cohort follow-up and data base maintenance), B (confirmation of cancer and cause of death), C (management of the biospecimens) and D (leadership and data analysis). The findings should enhance understanding of the etiology and progression of ovarian cancer and provide guidance for women and their health care providers in their efforts to reduce suffering and death from this disease.