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: 9265321
• 负责人: WILLIAM BLOT
• 金额: $ 19.23万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9265321
• 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; 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; cancer subtypes; 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，肥胖和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有关，但 绝经前妇女关于黑人妇女肥胖-乳腺癌协会的信息有限， 肥胖患病率最高的一组，三阴性（和基底样）乳腺的发病率较高 癌症），但管腔亚型的发病率较低。有可能是不一致的关联之间 黑人和白人的肥胖和乳腺癌风险可以通过他们的基础疾病的差异来解释。 肥胖与乳腺癌风险相关的机制。虽然这些机制不是 完全清楚的是，一般认为肥胖主要通过诱导胰岛素信号传导和抗性起作用， 增加雌激素的生物合成和炎症，增加患乳腺癌的风险。的相对 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不同， 这可能导致了不同亚型乳腺癌风险的种族差异。我们在此提出一个案例- 在前瞻性南方社区队列中嵌套的绝经后乳腺癌对照研究 这项研究跟踪了5万多名女性，其中三分之二是黑人，患有乳腺癌和其他癌症。 发病率。这一队列是从低收入人群中招募的，那里的肥胖很常见（58%的SCCS 黑人女性的BMI>30 kg/m2。具体目标是： 目标1.为了确定胰岛素样生长因子1，胰岛素样生长因子结合蛋白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/孕激素而不同 受体状态 目标2.为了确定肥胖状态是否上调肿瘤IGF 1信号，雌激素受体（ER） 信号和炎症基因表达特征增加乳腺癌风险，如果程度 上调因种族而异 目标3.为了确定诊断前循环中IGF 1、性激素和炎症水平是否 标记物与IGF 1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