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

项目总结 卵巢癌是美国女性癌症死亡的第五大原因。没有可靠的筛查 卵巢癌的早期检测方法已经存在，因此识别潜在的可改变的卵巢是至关重要的 癌症风险因素为预防策略提供信息。II型糖尿病是一种可预防的慢性疾病 在过去的几十年里，它的患病率一直在上升。II型糖尿病与更高的风险相关 然而，一些癌症的方法学挑战限制了先前对这种联系的研究。 II型糖尿病与卵巢癌风险之间的关系。这个应用程序的总体目标是前瞻性地检查 T2D、相关药物和生物标记物与卵巢癌总体风险和肿瘤风险的关系 特点。我们建议利用14项研究的资源来研究这些复杂的联系 参与卵巢癌队列联盟(OC3)，专门测试以下假设/目标： 目的1.研究T2D，包括诊断时的持续时间和年龄，与卵巢癌风险之间的关系。 总体而言，根据组织类型和肿瘤标记物的表达。 目的2.询问T2D治疗类型(例如，二甲双胍、胰岛素)的影响，以及治疗的变化 卵巢癌风险，总体上，按组织类型和肿瘤标记物表达。此外，我们还将研究是否 二甲双胍与每日小剂量阿司匹林联合使用对卵巢癌风险有协同作用 还原。 目的3.在探索性目标中，考察T2D定义的不同T2D“表型”之间的联系 相关生物标记物(空腹胰岛素、空腹血糖、HOMA-IR、脂联素)在一项嵌套病例对照研究中的应用 卵巢癌病例和对照。这一目的将使我们更清楚地了解机制(S) 潜在的T2D-卵巢癌关联。 拟议的研究将使用来自14项前瞻性队列研究的基线和后续数据，这些研究是 OC3。这包括100多万名妇女和5300例卵巢癌病例，这些病例来自已建立的预期队列 随访12-37年的研究。据我们所知，世界上没有其他卵巢癌联盟允许 对II型糖尿病、用药和相关的综合随访数据进行前瞻性评估 卵巢癌的危险因素。重要的是，阐明II型糖尿病与特定组织学之间的联系 亚型可能提供对卵巢癌发生的潜在机制的洞察，并具有 改进预防战略的潜力。

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.