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

项目摘要 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是存在的，因此识别潜在的可改变的卵巢癌是至关重要的。 癌症风险因素，以告知预防策略。II型糖尿病是一种可预防的慢性疾病， 在过去的几十年里，其流行率一直在上升。II型糖尿病与高风险相关， 然而，对于某些癌症，方法学上的挑战限制了先前研究的相关性， II型糖尿病和卵巢癌风险之间的关系。本申请的总体目标是前瞻性地检查 T2 D、相关药物和生物标志物与卵巢癌风险之间的关联，总体和肿瘤 特色我们建议利用14项研究的资源来研究这些复杂的关联 参与卵巢癌队列联盟（OC 3），具体测试以下假设/目标： 目标1.检查T2 D（包括诊断时的持续时间和年龄）与卵巢癌风险之间的关联， 总的来说，通过组织型和肿瘤标志物表达。 目标2.询问T2 D治疗类型的影响（例如，二甲双胍、胰岛素）和治疗变化， 卵巢癌的风险，总体而言，通过组织型，并通过肿瘤标志物表达。此外，我们将研究是否 二甲双胍联合每日低剂量阿司匹林对卵巢癌风险有协同作用 还原 目标3：在探索性目的中，检查T2 D定义的不同T2 D“表型”之间的关联 相关生物标志物（空腹胰岛素、空腹血糖、HOMA-IR、脂联素）的巢式病例对照研究， 卵巢癌病例和对照。这一目标将使我们能够更清楚地了解机制 T2 D与卵巢癌的关联。 这项拟议的研究将使用来自14项前瞻性队列研究的基线和随访数据，这些研究是 OC 3。这包括来自已建立的前瞻性队列的1，000，000多名女性和5，300多例卵巢癌病例 随访12-37年的研究。据我们所知，世界上没有其他卵巢癌协会允许 前瞻性评估，包括II型糖尿病、药物使用和相关的综合随访数据。 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 亚型可以提供对卵巢癌致癌的潜在机制的了解， 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.