Adiposity Related Biomarkers and Breast Tumor Size

肥胖相关生物标志物和乳腺肿瘤大小

• 批准号: 6515073
• 负责人: KATHLEEN E MALONE
• 金额: $ 8.54万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6515073
• 关键词: binding proteins; biomarker; breast neoplasms; clinical research; female; hormone regulation /control mechanism; human middle age (35-64); human subject; insulin; insulinlike growth factor; leptin; neoplasm /cancer invasiveness; neoplastic growth; obesity; prognosis; women's health; young adult human (21-34)

DESCRIPTION (Applicant's Description) An increasing number of reports substantiate that obesity is a risk factor for recurrence and mortality in breast cancer patients. Heavier women have an increased risk of recurrence or death, compared to thinner women, even after controlling for other prognostic factors. We hypothesize that women of greater body mass present with larger tumors (and ultimately a worse prognosis) due to the following endocrine- metabolizing hormones that are associated with obesity and that may mediate rapid breast tumor proliferation: leptin, type 1 insulin-like growth factor (IGF-1), insulin-like growth factor binding protein type 3 (IGFBP-3) and insulin. IGF-1, IGFBP-3 and insulin have all been associated with both increased breast cancer incidence and decreased survival from the disease. These hormones are associated with obesity either directly or through mediating pathways (e.g., growth hormone/IGF axis). Leptin levels are highly correlated with fat mass. Recently, two epidemiologic studies found a relationship between circulating leptin levels and breast cancer incidence. A population-based cohort of invasive breast cancer cases first identified through two large studies of breast cancer etiology in young women and now being followed for factors that affect survival serves as the underlying infrastructure for this project. Extensive information on participants has been collected, using detailed questionnaires, an extensive medical records review, as well as a histopathology review and molecular analysis of tumors. Plasma samples were collected from participants in the original studies and will be used to complete assays of the hormones of interest. For the proposed pilot study, a comparison will be made of hormone levels across groups defined by tumor size and body mass index (BMI) among young invasive breast cancer cases. Hormone levels will also be examined for their relationship with tumor prognostic markers. There is a critical need to elucidate possible biologic mechanisms underlying the poor prognosis associated with obesity in breast cancer patients. Findings from this study could begin to clarify a mechanism by which adiposity affects prognosis from breast cancer.

描述（申请人的描述） 报告数量不断增加 证实肥胖是复发和死亡的危险因素 乳腺癌患者。 体重较重的女性复发或复发的风险增加 与较瘦的女性相比，即使在控制其他预后因素后，死亡 因素。 我们假设体重较大的女性具有较大的 由于以下内分泌因素，肿瘤（最终预后更差） 与肥胖相关并可能介导的代谢激素 乳腺肿瘤快速增殖：瘦素、1 型胰岛素样生长因子 (IGF-1)、胰岛素样生长因子结合蛋白 3 型 (IGFBP-3) 和 胰岛素。 IGF-1、IGFBP-3 和胰岛素都与乳房增大有关 癌症发病率和该疾病的生存率降低。 这些激素是 与肥胖直接相关或通过中介途径（例如， 生长激素/IGF 轴）。 瘦素水平与脂肪量高度相关。 最近，两项流行病学研究发现，循环 瘦素水平和乳腺癌发病率。 首次发现基于人群的浸润性乳腺癌病例队列 通过两项针对年轻女性乳腺癌病因学的大型研究，现在 跟踪影响生存的因素作为潜在的 该项目的基础设施。 有关参与者的广泛信息 通过详细的调查问卷和广泛的医疗记录收集 审查，以及肿瘤的组织病理学审查和分子分析。 血浆样本是从原始研究的参与者那里收集的 将用于完成感兴趣激素的测定。 对于提议的 试点研究，将对定义的各组之间的激素水平进行比较 年轻浸润性乳腺癌的肿瘤大小和体重指数 (BMI) 案例。 还将检查激素水平与肿瘤的关系 预后标志物。 迫切需要阐明潜在的生物学机制 乳腺癌患者的不良预后与肥胖相关。 这项研究的结果可以开始阐明肥胖的机制 影响乳腺癌的预后。