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); 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）越来越多的报告 证实肥胖是复发和死亡率的危险因素 乳腺癌患者。 较重的妇女的复发风险增加或 死亡，与较薄的女性相比，即使在控制了其他预后之后 因素。 我们假设体重更大的女性较大 肿瘤（最终预后较差），由于以下内分泌 - 与肥胖相关的代谢激素，可能介导 快速乳腺肿瘤增殖：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加有关 癌症的发病率和疾病的生存降低。 这些激素是 与肥胖直接或通过介导途径相关（例如， 生长激素/IGF轴）。 瘦素水平与脂肪质量高度相关。 最近，两项流行病学研究发现循环之间有关系 瘦素水平和乳腺癌发病率。 首先确定的基于人群的侵入性乳腺癌病例 通过对年轻女性乳腺癌病因的两项大型研究，现在 遵循影响生存的因素作为基础 该项目的基础架构。 有关参与者的大量信息 使用详细的问卷收集了广泛的医疗记录 综述，以及肿瘤的组织病理学综述和分子分析。 从原始研究的参与者那里收集血浆样本，并 将用于完成感兴趣的激素的测定。 对于拟议的 试点研究，将比较定义的组之间的激素水平 年轻的侵入性乳腺癌中的肿瘤大小和体重指数（BMI） 案例。 激素水平也将检查其与肿瘤的关系 预后标记。 迫切需要阐明潜在的生物学机制 乳腺癌患者中与肥胖有关的预后不良。 这项研究的发现可以开始阐明一种肥胖的机制 影响乳腺癌的预后。