The obesity-metabolic biomarker axis and breast cancer risk

肥胖代谢生物标志物轴与乳腺癌风险

• 批准号: 8923154
• 负责人: WILLIAM BLOT
• 金额: $ 20.99万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2016-04-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8923154
• 关键词: Adipose tissue; Anabolism; Anti-Inflammatory Agents; Anti-inflammatory; Biological Markers; Biopsy; Blood; Blood specimen; Breast; Breast Cancer Prevention; C-reactive protein; Case-Control Studies; Cohort Studies; Communities; Comorbidity; Complex; Data; Development; Diabetes Mellitus; Diagnostic; Employee Strikes; Epidemiologic Studies; Estradiol; Estrogen Receptors; Estrogens; Estrone; Gene Expression Profile; Gonadal Steroid Hormones; High Prevalence; Incidence; Inflammation; Inflammatory; Instruction; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Joints; Knowledge; Leptin; Low Income Population; Malignant Neoplasms; Mammary Gland Parenchyma; Metabolic; Modeling; Normal tissue morphology; Obesity; Pathogenesis; Pathway interactions; Positioning Attribute; Postmenopause; Premenopause; Progesterone Receptor Status; Publishing; Race; Receptor Signaling; Recruitment Activity; Relative (related person); Research; Risk; Risk Estimate; Risk Marker; Sampling; Serum; Sex Hormone-Binding Globulin; Signal Transduction; Subgroup; Testing; Testosterone; Time; Tissue Sample; Tissues; Tumor Tissue; Up-Regulation; Variant; Woman; Women' s Group; adiponectin; cancer risk; case control; cohort; cytokine; indexing; inflammatory marker; insulin signaling; malignant breast neoplasm; novel; obesity risk; prospective; racial difference; tumor

Existing epidemiologic studies suggest a complex relationship between obesity and breast cancer, with obesity generally associated with increased risk among postmenopausal women but reduced risk among premenopausal women. Limited information exists on the obesity-breast cancer association for black women, the group with the highest prevalence of obesity, higher incidence of triple negative (and basal-like) breast cancer), but lower incidence of the luminal subtype. It is possible that inconsistent associations between obesity and breast cancer risk in blacks and whites are explained by their differences in underlying mechanisms through which obesity is related to breast cancer risk. Although these mechanisms are not entirely clear, it is in general believed that obesity acts primarily by inducing insulin signaling and resistance, increased estrogen biosynthesis and inflammation to increase the risk of breast cancer. The relative contribution of these mechanisms to the pathogenesis of breast cancer may differ between blacks and whites, which may contribute to racial difference in risk of breast cancer by subtype. We propose herein a case- control study of postmenopausal breast cancer nested within the prospective Southern Community Cohort Study that is tracking over 50,000 women, two-thirds of whom are black, for breast and other cancer incidence. This cohort was recruited from a low-income population where obesity is common (58% of SCCS black women have a BMI>30 kg/m^. Specific aims are: Aim 1. To determine whether circulating levels of IGF1, IGF-binding protein 3, adiponectin, leptin, CRP and sex hormones [estradiol, estrone, testosterone and sex hormone-binding globulin (SHBG)] are associated with risk of postmenopausal breast cancer, and whether they differ by race and/or tumor estrogen/progesterone receptor status. Aim 2. To determine whether the obese state upregulates tumor IGF1 signaling, estrogen receptor (ER) signaling and inflammation gene expression signatures to increase breast cancer risk, and if the extent of upregulation differs by race Aim 3. To determine whether pre-diagnostic circulating levels of IGF1, sex hormones and inflammation markers are associated with IGF1 signaling, ER signaling and inflammation gene expression signatures, respectively, in breast cancer tissues

现有的流行病学研究表明肥胖与乳腺癌之间存在复杂的关系， 肥胖通常与绝经后妇女的风险增加相关，但与绝经后妇女的风险降低相关 绝经前妇女。关于黑人女性肥胖与乳腺癌关联的信息有限， 肥胖患病率最高的群体，三阴性（和基底样）乳腺发生率较高 癌症），但管腔亚型的发病率较低。之间的关联可能不一致 黑人和白人的肥胖和乳腺癌风险是由他们的潜在差异来解释的 肥胖与乳腺癌风险相关的机制。虽然这些机制不 完全清楚，人们普遍认为肥胖主要通过诱导胰岛素信号传导和抵抗来起作用， 增加雌激素生物合成和炎症，增加患乳腺癌的风险。亲戚 这些机制对乳腺癌发病机制的贡献在黑人和白人之间可能有所不同， 这可能导致不同亚型的乳腺癌风险存在种族差异。我们在此提出一个案例—— 前瞻性南方社区队列中绝经后乳腺癌的对照研究 研究正在追踪超过 50,000 名女性（其中三分之二是黑人）的乳腺癌和其他癌症情况 发生率。该队列是从肥胖常见的低收入人群中招募的（58% 的 SCCS 黑人女性的 BMI>30 kg/m^。具体目标是： 目的 1. 确定 IGF1、IGF 结合蛋白 3、脂联素、瘦素、CRP 和 性激素 [雌二醇、雌酮、睾酮和性激素结合球蛋白 (SHBG)] 与 绝经后乳腺癌的风险，以及它们是否因种族和/或肿瘤雌激素/孕激素而异 受体状态。 目标 2. 确定肥胖状态是否上调肿瘤 IGF1 信号、雌激素受体 (ER) 信号传导和炎症基因表达特征会增加乳腺癌风险，并且如果程度 上调因种族而异 目标 3. 确定诊断前 IGF1、性激素和炎症的循环水平是否 标记物与 IGF1 信号传导、ER 信号传导和炎症基因表达特征相关， 分别在乳腺癌组织中