Type II diabetes, related biomarkers and medications, and ovarian cancer risk

II 型糖尿病、相关生物标志物和药物以及卵巢癌风险

• 批准号: 10357268
• 负责人: Holly Ruth Harris
• 金额: --
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10357268
• 关键词: Adult; Age; Aspirin; Biological; Biological Markers; Body mass index; Cancer Etiology; Cessation of life; Characteristics; Chemoprevention; Chronic Disease; Clinical Trials; Colorectal Cancer; Complex; Data; Development; Diabetes Mellitus; Diagnosis; Disease; Disease Pathway; Dose; Endometrial Carcinoma; Evaluation; Fasting; Future; Goals; Histologic; Hyperglycemia; Hyperinsulinism; Incidence; Inflammation; Insulin; Insulin Resistance; Malignant Neoplasms; Malignant neoplasm of liver; Malignant neoplasm of ovary; Malignant neoplasm of pancreas; Mediating; Mendelian randomization; Metabolic; Metabolic Pathway; Metabolic dysfunction; Metformin; Methodology; Methods; Nested Case-Control Study; Non-Insulin-Dependent Diabetes Mellitus; North America; Obesity; Obesity Epidemic; Pathway interactions; Pharmaceutical Preparations; Phenotype; Prevalence; Prevention strategy; Prognosis; Prospective cohort study; Research; Resources; Risk; Risk Factors; Risk Reduction; Screening for Ovarian Cancer; Somatomedins; Testing; Tumor Markers; Tumor Subtype; Tumor Tissue; Tumor-associated macrophages; United States; Woman; Work; adiponectin; cancer risk; cancer therapy; carcinogenesis; case control; cohort; diabetes mellitus therapy; fasting glucose; follow-up; high risk; improved; insight; malignant breast neoplasm; non-diabetic; prospective; prostate cancer risk; screening; tissue biomarkers; treatment strategy; tumor; young adult

PROJECT SUMMARY Ovarian cancer is the 5th leading cause of cancer death among women in the United States. No reliable screening method exists for the early detection of ovarian cancer thus it is critical to identify potentially modifiable ovarian cancer risk factors to inform prevention strategies. Type II diabetes is a preventable chronic disease and over the past few decades its prevalence has been rising. Type II diabetes has been associated with higher risks of some cancers, however methodologic challenges have limited previous studies examining the association between type II diabetes and ovarian cancer risk. The overall goal of this application is to prospectively examine the association between T2D, related medications and biomarkers, and ovarian cancer risk, overall and by tumor characteristics. We propose to examine these complex associations by leveraging resources from 14 studies participating in the Ovarian Cancer Cohort Consortium (OC3), specifically testing the following hypotheses/aims: Aim 1. Examine the association between T2D, including duration and age at diagnosis, and ovarian cancer risk, overall, by histotype, and by tumor marker expression. Aim 2. Interrogate the impact of type of T2D therapy (e.g., metformin, insulin), and changes in therapy, on ovarian cancer risk, overall, by histotype, and by tumor marker expression. In addition, we will examine whether metformin use in combination with low-dose daily aspirin use has a synergistic impact on ovarian cancer risk reduction. Aim 3. In an exploratory aim, examine the associations between different T2D “phenotypes” as defined by T2D related biomarkers (fasting insulin, fasting glucose, HOMA-IR, adiponectin) in a nested case-control study of ovarian cancer cases and controls. This aim will allow us to more clearly understand the mechanism(s) underlying the T2D-ovarian cancer association. The proposed study will use baseline and follow-up data from 14 prospective cohort studies that are part of the OC3. This includes over 1,000,000 women and 5,300+ ovarian cancer cases from established prospective cohort studies with 12-37 years of follow-up. We know of no other ovarian cancer consortia in the world that permits prospective evaluation with comprehensive follow-up data on type II diabetes, medication use, and relevant ovarian cancer risk factors. Importantly, clarifying the association between type II diabetes and specific histologic subtypes may provide insight into the underlying mechanisms of ovarian cancer carcinogenesis and has the potential to improve prevention strategies.

项目摘要 卵巢癌是美国女性癌症死亡的第五个主要原因。没有可靠的筛选 存在早期检测卵巢癌的方法，因此鉴定潜在可修饰的卵巢至关重要 为预防策略提供信息的癌症风险因素。 II型糖尿病是一种可预防的慢性疾病，超过了 在过去的几十年中，其流行率一直在上升。 II型糖尿病与更高的风险有关 一些癌症，但是方法论挑战限制了先前研究关联的研究 在II型糖尿病和卵巢癌风险之间。该应用的总体目标是前瞻性检查 T2D，相关药物和生物标志物以及卵巢癌风险之间的关联，整体和肿瘤 特征。我们建议通过利用14项研究的资源来检查这些复杂的关联 参加卵巢癌队列联盟（OC3），专门检验以下假设/目标： AIM 1。检查T2D之间的关联，包括诊断时持续时间和年龄，以及卵巢癌风险， 总体而言，通过组织型和肿瘤标记表达。 目标2。询问T2D疗法类型（例如，二甲双胍，胰岛素）的影响，治疗的变化，对 总体而言，卵巢癌风险是通过组织型和肿瘤标记表达的。此外，我们将检查是否 二甲双胍与低剂量的每日使用阿司匹林使用对卵巢癌风险有协同影响 减少。 目标3。在探索性目的中，检查T2D定义的不同T2D“表型”之间的关联 相关的生物标志物（禁食胰岛素，禁食葡萄糖，HOMA-IR，脂联素） 卵巢癌病例和对照。这个目标将使我们能够更清楚地了解机制 T2D-ovarian癌症协会的基础。 拟议的研究将使用14项前瞻性队列研究的基线和后续数据，这些数据是该研究的一部分 OC3。其中包括已建立的预期队列的100万妇女和5,300多个卵巢癌病例 随访12 - 37年的研究。我们知道世界上没有其他卵巢癌财团可以允许 预期评估以及有关II型糖尿病，药物使用和相关的全面随访数据 卵巢癌风险因素。重要的是，阐明II型糖尿病与特定组织学之间的关联 亚型可以提供对卵巢癌致癌的潜在机制的见解，并具有 提高预防策略的潜力。