Using biomarkers to elucidate the breastfeeding and ovarian cancer risk association

使用生物标志物阐明母乳喂养和卵巢癌风险关联

• 批准号: 10579832
• 负责人: Naoko Sasamoto
• 金额: $ 8.95万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-07 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10579832
• 关键词: Adult; Age; Amenorrhea; Anti-Inflammatory Agents; Aspirin; Biological; Biological Assay; Biological Markers; Blood; Body mass index; Breast Feeding; CD3 Antigens; CD8B1 gene; Cancer Etiology; Case/Control Studies; Cells; Chemoprevention; Cholesterol; Contraceptive Usage; Cytotoxic T-Lymphocytes; Data; Diagnosis; Diagnostic; Disease; Environment; Equilibrium; Ethnic Origin; FOXP3 gene; Family history of; Future; Goals; Immune; Immunofluorescence Immunologic; Immunologic Markers; Infiltration; Inflammatory; Interleukin-6; International; Intervention; Lipids; Low-Density Lipoproteins; Lysophosphatidylcholines; Malignant neoplasm of ovary; Measures; Mediating; Metabolic; Metabolic Diseases; Metabolic Marker; Metabolic Pathway; Metabolism; Methods; New England; Non-Steroidal Anti-Inflammatory Agents; Nurses' Health Study; Obesity; Oral Contraceptives; Ovarian; Ovulation; Participant; Pathway interactions; Postpartum Period; Prevention Research; Prevention strategy; Prospective cohort; Prospective, cohort study; Questionnaires; Race; Recording of previous events; Regulatory T-Lymphocyte; Reporting; Reproducibility; Research; Resources; Risk; Risk Factors; Risk Reduction; Sampling; Serum; Sphingomyelins; Tissues; Tumor Immunity; Tumor Markers; Tumor Tissue; Tumor-associated macrophages; Woman; cancer diagnosis; cancer risk; cancer survival; carcinogenesis; case control; circulating biomarkers; cytokine; epidemiology study; improved; improved outcome; inflammatory marker; innovation; insight; lactational amenorrhea; new therapeutic target; novel; ovarian cancer prevention; ovarian neoplasm; parity; population based; preventive intervention; prospective; systemic inflammatory response; tumor

ABSTRACT Ovarian cancer survival is poor with a 5-year survival of less than 50% and has shown little improvement in the past several decades. Prevention of ovarian cancer has been challenging due to the lack of truly modifiable factors that reduce ovarian cancer risk. Breastfeeding is associated with decreased ovarian cancer risk; however, little is known about the biologic pathways impacted by breastfeeding that leads to long-term reduction in ovarian cancer risk. The goal of this application is to elucidate the association between breastfeeding and reduced ovarian cancer risk by identifying factors that mediate and modify this association. While breastfeeding can cause amenorrhea which decreases the lifetime number of ovulations, the observed protection exceeds what would be expected by lactational amenorrhea alone. We hypothesize that breastfeeding alters the metabolic, inflammatory, and immune environment both locally and systemically and these changes persist for years after the exposure, leading to decreased ovarian cancer risk. To examine these mechanisms, we will leverage existing detailed questionnaire data from two international consortia including 854,050 women across 22 studies (12 case-control studies including 9,357 cases, 12,425 controls and 10 prospective cohorts including 832,268 participants with 1,900 cases), circulating inflammatory and metabolic biomarker data measured in prospectively collected samples from more than 7,000 participants in the Nurses’ Health Studies (NHS/NHSII), and ovarian cancer tumor tissue marker data from 681 ovarian cancer cases in NHS/NHSII and the population-based New England Case Control Study (NEC). This innovative project will leverage data from two international consortia, blood biomarker data generated using reproducible validated assays, and tissue marker data using the cutting edge, multiplex immunofluorescence platform that allows simultaneous consideration of multiple immune markers. These extensive resources and rigorous methods provide a unique opportunity to investigate several mechanisms that may help explain the long-term impact of breastfeeding on ovarian cancer risk reduction. Results from this project will enhance our understanding of the underlying biologic pathways through which breastfeeding reduces ovarian cancer risk, opening new avenues for ovarian cancer prevention research. Importantly, findings from the proposed research have high potential to inform novel prevention strategies through identification of key inflammatory, immune, and metabolic pathways modulated by breastfeeding and thus greatly improve outcomes for women diagnosed with this deadly disease.

抽象的 卵巢癌的存活率较差，5年生存率少于50％，并且显示出几乎没有改善 过去几十年。由于缺乏真正的修改，预防卵巢癌受到挑战 减少卵巢癌风险的因素。母乳喂养与卵巢癌风险降低有关；然而， 关于母乳喂养影响的生物学途径知之甚少，母乳喂养会导致卵巢长期减少 癌症风险。该应用的目的是阐明母乳喂养和减少的关联 卵巢癌通过识别介导和修改这种关联的因素来风险。母乳喂养可能导致 减少排卵寿命数量的闭经，观察到的保护超过了 仅由泌乳性闭经预期。我们假设母乳喂养改变了代谢， 炎症和免疫环境在本地和系统上，这些变化持续多年 暴露导致卵巢癌风险降低。为了检查这些机制，我们将利用现有的 来自两个国际财团的详细调查表数据，包括22项研究中的854,050名妇女（12个 病例对照研究，包括9,357例病例，12,425个对照和10个前瞻性队列，包括832,268 有1,900例），循环炎症和代谢生物标志物数据的参与者。 从护士健康研究（NHS/NHSII）和卵巢中收集了7,000多名参与者的样本 NHS/NHSII中681例卵巢癌病例的癌症肿瘤组织标记数据和基于人群的新型 英格兰案例控制研究（NEC）。这个创新的项目将利用来自两个国际财团的数据， 使用可重现的经过验证的测定产生的血液生物标志物数据，以及使用切割的组织标记数据 边缘，多重免疫荧光平台，可以简单考虑多种免疫 标记。这些广泛的资源和严格的方法为调查几个 可能有助于解释母乳喂养对卵巢癌风险降低的长期影响的机制。 该项目的结果将增强我们对潜在生物学途径的理解 母乳喂养降低了卵巢癌的风险，为卵巢癌预防研究开辟了新的途径。 重要的是，拟议研究的发现具有很高的潜力，可以为新颖的预防策略提供信息 通过鉴定由母乳喂养和 因此，对于被诊断出患有这种致命疾病的妇女而言，取得了很大的改善。