Changing Contraceptive Patterns and Ovarian Cancer Risk

改变避孕方式和卵巢癌风险

• 批准号: 10184558
• 负责人: Kathryn L. Terry
• 金额: $ 52.82万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10184558
• 关键词: Address; African American; Age; Attenuated; Biological; Birth; CD3 Antigens; CD8B1 gene; Case-Control Studies; Cells; Clear Cell; Cohort Studies; Contraceptive Agents; Contraceptive Usage; Contraceptive methods; Cytotoxic T-Lymphocytes; Data; Disease; Endometrial Carcinoma; Enrollment; FOXP3 gene; First Births; Focal Infection; Future; Heme; High Prevalence; Histologic; Hormonal; Immune; Immune response; Immunofluorescence Immunologic; Immunologic Markers; Incidence; Infiltration; Inflammation; Intrauterine Devices; Lead; Link; Malignant neoplasm of ovary; Measures; Meta-Analysis; Molecular; Nature; New England; Nulliparity; Oral Contraceptives; Ovarian; Participant; Pathogenesis; Pathway interactions; Pattern; Physiological; Play; Population; Population Study; Premalignant Cell; Progesterone; Prospective cohort; Public Health; Race; Regulatory T-Lymphocyte; Reporting; Research; Resources; Risk; Risk Estimate; Risk Factors; Role; Sample Size; Serous; Steroid Receptors; Stromal Neoplasm; Subgroup; Technology; Time; Tissue Microarray; Tissues; Tumor Subtype; Update; Woman; Women' s Health; aged; cancer epidemiology; cancer risk; cancer subtypes; carcinogenesis; case control; cell type; cohort; epidemiology study; innovation; macrophage; modifiable risk; neoplastic cell; ovarian neoplasm; prospective; protective effect; protective factors; receptor expression; reproductive; scavenger receptor; trend; tumor; tumor microenvironment; tumor-immune system interactions

ABSTRACT Contraceptive patterns are changing and the implications for ovarian cancer risk are unknown. Oral contraceptives (OCs), which are an established protective factor for ovarian cancer, are being used less frequently and intrauterine device use (IUD) is on the rise. However, the impact of changing contraceptive patterns on ovarian cancer incidence is unclear. While most studies of IUDs and ovarian cancer risk suggest an inverse association, some studies report no association or even a slight increase in risk. Differences between these studies could be attributable to IUD type, timing, or molecular features of tumors including histotypes. Preliminary data from the New England Case Control (NEC) Study suggest the association between IUDs and ovarian cancer risk vary by histotype, with a non-significant decrease in risk of low-grade serous and clear cell tumors but not for other histotypes. Furthermore, we observed an increased risk of ovarian cancer with low tumor stromal CD163 expression, reflecting heme scavenger receptor expression decreased M2-type macrophage infiltration. These observations suggest the impact of IUD use on ovarian cancer risk may differ by subtype and subgroup, but larger samples sizes are needed. Inflammation is known to play a role in ovarian cancer pathogenesis, and IUDs exert their physiologic effect through local inflammation. However, IUD-associated inflammation may be accompanied by an immune response that could lead to clearance of premalignant cells or local infection. An appreciation of how ovarian cancer risk varies by expression of immune markers within tumors may inform the biologic mechanisms possibly involved (e.g. CD3, CD8, CD4, CD69, FOXP3, CD163). Here we propose to evaluate the association between IUD use and ovarian cancer risk in 17 case control studies and 7 cohort studies with a total of more than 20,000 cases that collected, with varying degrees of detail, data on IUD type and timing of use (e.g. age at use and before/after first birth), as well as detailed histologic data critical for distinguishing ovarian cancer subtypes. Importantly, our proposed research includes a case-control study of African American women enrolled between 2010-2015, reflecting recent contraceptive trends and increasing diversity. The inclusion of cohort studies with updated contraceptive use data and a case-control study which recently completed enrollment will provide information on the contemporary contraceptive use. Furthermore, we will utilize unique resources and innovative platforms to examine the potential mechanisms through which contraceptive choice influences ovarian cancer risk. In more than 3,000 cases with detailed contraceptive data, we will simultaneously measure a panel of immune markers by multiplex immunofluorescence which shows co-localization of marker expression. Both the high prevalence and modifiable nature of contraceptive use make this an important public health question with a significant impact on the population burden of ovarian cancer.

抽象的 避孕模式正在发生变化，对卵巢癌风险的影响尚不清楚。口服 避孕药（OCS）是卵巢癌的既定保护因素，正在使用较少 通常，宫内设备的使用（IUD）在上升。但是，改变避孕药的影响 卵巢癌发病率的模式尚不清楚。虽然大多数关于宫内节育器和卵巢癌风险的研究表明 逆关联，一些研究报告没有关联甚至风险略有增加。差异 在这些研究之间，可能归因于肿瘤的宫内宫内节育器类型，时机或分子特征 组织型。新英格兰案例控制（NEC）研究的初步数据表明了关联 在宫内节育器和卵巢癌之间因组织型而异，低级风险降低了 浆液性细胞肿瘤，但不适合其他组织型。此外，我们观察到了 卵巢癌具有低肿瘤基质CD163表达，反映了血红素清除剂受体表达 M2型巨噬细胞浸润降低。这些观察结果表明，宫内节育器对卵巢的影响 癌症风险可能因亚型和亚组而有所不同，但需要较大的样品尺寸。炎症是已知的 在卵巢癌发病机理中发挥作用，宫内节育器通过局部发挥其生理作用 炎。但是，IUD相关的炎症可能伴随着免疫反应 可能导致预灭p细胞或局部感染的清除。对卵巢癌的风险的欣赏 因肿瘤中免疫标记的表达而有所不同，可能会告知可能涉及的生物学机制 （例如CD3，CD8，CD4，CD69，FOXP3，CD163）。在这里，我们建议评估宫内节期间使用之间的关联 17例病例对照研究和7个队列研究中的卵巢癌风险，总共超过20,000例 收集的，具有不同程度的详细信息，有关宫内节育器类型和使用时间的数据（例如，使用年龄和 在第一次出生之前/之后），以及对区分卵巢癌亚型至关重要的详细组织学数据。 重要的是，我们拟议的研究包括一项对非裔美国妇女的案件对照研究 在2010年至2015年之间，反映了最近的避孕趋势和增加的多样性。包括队列 使用更新的避孕药使用数据和最近完成入学的病例对照研究的研究将 提供有关当代避孕药使用的信息。此外，我们将利用独特的资源和 创新平台，以检查避孕选择影响的潜在机制 卵巢癌风险。在3,000多个具有详细避孕数据的案例中，我们将同时测量 通过多重免疫荧光的一个免疫标记面板，显示标记的共定位 表达。避孕药使用的高流行率和可修改的性质使得这很重要 公共卫生问题对卵巢癌的人口负担有重大影响。