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 卵巢癌的生存率很差，5年生存率低于50%，并且在生存方面几乎没有改善。 过去几十年来，由于缺乏真正可改变的方法，卵巢癌的预防一直具有挑战性。 然而，降低卵巢癌风险的因素与卵巢癌风险相关。 对于母乳喂养影响导致卵巢功能长期减少的生物学途径知之甚少 该应用的目的是阐明母乳喂养与降低癌症风险之间的关联。 通过识别介导和改变这种关联的因素来增加卵巢癌的风险，而母乳喂养可能会导致卵巢癌。 闭经会减少终生排卵次数，观察到的保护作用超过了预期的保护作用 我们认为母乳喂养会改变新陈代谢， 局部和全身的炎症和免疫环境，这些变化在术后持续多年 暴露，导致卵巢癌风险降低 为了检查这些机制，我们将利用现有的机制。 来自两个国际联盟的详细问卷数据，包括 22 项研究中的 854,050 名女性（12 病例对照研究包括 9,357 例病例、12,425 名对照者和 10 个前瞻性队列（包括 832,268 名患者） 1,900 例参与者），前瞻性测量的循环炎症和代谢生物标志物数据 从护士健康研究 (NHS/NHSII) 的 7,000 多名参与者收集了样本，并且卵巢 来自 NHS/NHSII 和基于人群的 681 例卵巢癌病例的癌症肿瘤组织标志物数据 英格兰病例对照研究 (NEC) 该创新项目将利用来自两个国际联盟的数据： 使用可重复的验证测定生成的血液生物标志物数据，以及使用切割生成的组织标志物数据 边缘多重免疫荧光平台，允许同时考虑多种免疫 这些广泛的资源和严格的方法为研究多种标记提供了独特的机会。 可能有助于解释母乳喂养对降低卵巢癌风险的长期影响的机制。 该项目的结果将增强我们对潜在生物学途径的理解 母乳喂养可降低卵巢癌风险，为卵巢癌预防研究开辟新途径。 重要的是，拟议研究的结果很有可能为新的预防策略提供信息 通过识别母乳喂养和调节的关键炎症、免疫和代谢途径 从而大大改善被诊断患有这种致命疾病的女性的治疗结果。