Ovarian Cancer

在本项目中，我们建议继续调查潜在的可改变的营养和激素风险 卵巢癌的发病因素这项工作将使用前瞻性收集的问卷数据，生物 样本和石蜡包埋的卵巢肿瘤组织，来自护士健康研究（NHS）的女性， NHSII。虽然关于卵巢癌病因的几种假说已经提出，但很少有可修改的。 生活方式的风险因素已经确定。我们将研究维生素D可能的预防作用， 卵巢癌，目的是确定哪些亚群可以从干预中获益最多。我们 还将评估三个饮食因素：类黄酮，这可能会降低风险;乳糖在青春期， 成年;丙烯酰胺摄入量和红细胞加合物水平，两者都可能增加风险。我们也 将评估褪黑激素和轮班工作在卵巢癌发生中的作用。此外，我们建议 测量炎症的循环标志物（CPR、IL-6和TNFa-R2）和与炎症相关的肿瘤标志物。 炎症（例如，STAT）。我们还首次提出专门关注致命的卵巢癌， 努力确定可能使妇女易患快速生长肿瘤或 腹膜环境易发生转移。同样，我们计划评估激素受体 在卵巢肿瘤中的作用及其与危险因素的关系，重点是探索一种新的卵巢肿瘤模型。 致癌作用（缓慢生长的肿瘤与快速生长的肿瘤）作为流行病学中肿瘤分类的一种方法 问题研究该项目与项目1和2有共同的生物学主题，包括维生素D的作用， 褪黑激素和炎症途径，并与项目4密切相互作用的方法学问题。它还 与其他项目共享Cores 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（确认癌症和死亡原因），C （生物标本的管理）和D（领导和数据分析）。调查结果应能增强 了解卵巢癌的病因和进展，并为妇女及其 卫生保健提供者努力减少这种疾病的痛苦和死亡。

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.