Characteristics of tubal ligation and risk of epithelial ovarian cancer

输卵管结扎的特点与上皮性卵巢癌的风险

• 批准号: 8261328
• 负责人: Shelley S Tworoger
• 金额: $ 9.62万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8261328
• 关键词: Address; Age; Antibodies; Biological; Cancer Etiology; Cauterization - action; Cells; Cessation of life; Characteristics; Child; Cohort Studies; Contraceptive Usage; Data; Disease; Distal; Effectiveness; Epithelial ovarian cancer; Epithelium; Evaluation; Family history of; Genital system; High Risk Woman; Histologic; Histology; Hormones; Human; Immunity; Individual; Inflammatory; Institutes; Interruption; Lead; Life Style; Ligation; Local anesthesia; Malignant Neoplasms; Malignant neoplasm of ovary; Mammalian Oviducts; Mediating; Medical; Membrane Glycoproteins; Modeling; Mucin 1 protein; Nurses' Health Study; Operative Surgical Procedures; Oral Contraceptives; Ovarian; Ovary; Ovulation; PTGS2 gene; Paraffin Embedding; Pelvis; Population; Prevention; Preventive; Primary Prevention; Procedures; Process; Production; Questionnaires; Recommendation; Reporting; Resources; Risk; Risk Factors; Risk Reduction; Role; STAT3 gene; Selection Bias; Serous; Site; Subgroup; Surface; Talc; Time; Tissues; Tubal Ligation; Tumor Tissue; Tumor-Derived; Weight; Woman; Work; cancer risk; cohort; disorder risk; follow-up; high risk; improved; inflammatory marker; insight; lifestyle factors; malignant breast neoplasm; modifiable risk; ovarian cancer prevention; ovarian neoplasm; overexpression; prospective; protective effect; protein expression; public health relevance; theories; tumor

DESCRIPTION (provided by applicant): ABSTRACT Although a strong inverse association has been observed between tubal ligation and epithelial ovarian cancer risk, it is unclear how long the protection from a tubal ligation lasts, or whether the inverse association is stronger for, or observed only in, specific subgroups of women. Further, the underlying biological mechanisms responsible for the protective effects of this procedure are unclear. Therefore, in this application, we will conduct a detailed evaluation of tubal ligation with ovarian cancer risk. In this study, we propose to re-examine tubal ligation as an important risk factor for epithelial ovarian cancer, and specifically, to evaluate a modifying role of both surgery-related and other lifestyle choices (e.g., oral contraceptive use, genital talc use, and individual risk of ovarian cancer) as well as tumor characteristics. In addition, we plan to assess whether the cancer protective effects of tubal ligation are mediated via inflammatory processes or MUC1-associated immunity. Using prospectively collected questionnaire data and paraffin-embedded ovarian tumor tissue already collected from women in the Nurses' Health Study (NHS) and NHSII, two large prospective cohort studies initiated in 1976 (n=121,700) and 1989 (n=116,430), respectively, we propose to investigate a role of tubal ligation and potentially important mechanisms in detail. Over the course of follow-up (1976-2010 in NHS and 1989-2009 in NHS II) we expect to accrue 1,215 confirmed cases of epithelial ovarian cancer, of which 506 will have tumor tissue available. With the unique and prospectively-collected resources of these two cohorts, we will identify populations who can most benefit from tubal ligation in relation to ovarian cancer risk as well as elucidate the timing of when the surgery may be most protective - this could lead to important changes in prevention recommendations that could be instituted in the short term. In addition we will examine whether the inverse association of tubal ligation varies by histologic subtype, putative cell of origin (e.g., for tumors derived from the distal fallopian tube rather than the ovarian surface epithelium), or expression of inflammatory markers in the tumor (phosphorylated STAT3 (pSTAT3), pSTAT5, COX-2, MUC1). Given the weight of evidence that tubal ligation reduces risk of this disease, it is imperative to understand why and how this procedure confers protection, as well as whether characteristics of the surgery, woman, or tumor impact the effectiveness of tubal ligation. If these questions are addressed, there are potential implications for improving ovarian cancer prevention recommendations regarding tubal ligation. Further, examining the biological mechanisms underlying the protective effect of this common procedure will hopefully lead to other avenues of prevention that may be less invasive than having a tubal ligation. PUBLIC HEALTH RELEVANCE: PROJECT NARRATIVE Tubal ligation reduces risk of epithelial ovarian cancer, in this application we will examine why and how this procedure confers protection, as well as whether characteristics of the surgery, woman, or tumor impact the effectiveness of tubal ligation. This can be used to improve prevention recommendations for women at high risk of this disease.

描述（由申请人提供）：摘要尽管在输卵管结扎和上皮卵巢癌风险之间观察到了较强的逆关联，但目前尚不清楚在管结扎中的保护持续多长时间，或者逆关联是否更牢固，或者仅观察到特定女性亚组。此外，尚不清楚负责该程序保护作用的基本生物学机制。因此，在此应用中，我们将对具有卵巢癌风险的输卵管结扎术进行详细评估。在这项研究中，我们建议将管状结扎作为上皮性卵巢癌的重要危险因素，特别是评估与手术相关和其他生活方式选择的修改作用（例如，口腔避孕药，生殖器使用，生殖器滑石的使用，以及卵巢癌的个体风险）以及卵巢癌的个体特征。此外，我们计划评估输卵管结扎的癌症保护作用是通过炎症过程还是与MUC1相关的免疫来介导。使用前瞻性收集的问卷数据以及在护士健康研究（NHS）和NHSII中已经从女性那里收集的石蜡肿瘤组织和NHSII，这是1976年启动的两项大型前瞻性队列研究（n = 121,700）和1989年（n = 116,430）（n = 116,430），我们分别提出了一个详细的机制，并详细介绍了dubal ligniation and dubal ligniation and dubal ligniation and of dubal ligition and os os os os os os os os os os os os os os os os os os os os os os os os os os os os dubal。在随访的过程中（1976-2010在NHS和1989 - 2009年在NHS II中），我们期望有1,215例确认的上皮卵巢癌病例，其中506例将有可用的肿瘤组织。借助这两个队列的独特和前瞻性的资源，我们将确定可以从卵巢癌风险中最大的结扎中受益最大的人群，并阐明手术何时可能是最具保护性的时间 - 这可能会导致预防建议的重要变化，这些建议可以在短期内提出。此外，我们将检查输管结扎的反相关性是组织学亚型，推定的原始细胞（例如，对于源自远端输卵管而不是卵巢表面上皮的肿瘤）还是肿瘤中炎症标记的表达（磷酸化的Stat3（PSTAT3）（PSTAT3），PSTAT55，COX5，COX-1，MUC1，MUC1，MUC，考虑到大量证据表明输卵管结扎降低了这种疾病的风险，因此必须了解该过程的原因以及如何赋予保护，以及手术，女性或肿瘤的特征是否会影响输卵管结扎的有效性。如果解决了这些问题，则可能对改善有关输卵管结扎的卵巢癌预防建议有潜在的影响。此外，检查这种常见程序保护作用的生物学机制将有望导致其他预防途径，而预防途径可能不如进行管结扎剂。 公共卫生相关性：项目叙事管结扎降低了上皮卵巢癌的风险，在本应用中，我们将研究为什么以及该过程如何赋予保护，以及手术，女性或肿瘤的特征是否会影响输卵管结扎的有效性。这可用于改善这种疾病高风险的女性预防建议。