Obesity and IGF-axis Activation in Native Hawaiian Women with Breast Cancer

患有乳腺癌的夏威夷原住民妇女的肥胖和 IGF 轴激活

• 批准号: 8774560
• 负责人: LENORA WM LOO
• 金额: $ 16.53万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-08 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8774560
• 关键词: Address; African American; Age; Apoptosis; Archives; Asians; Bioavailable; Biological; Biological Assay; Biological Factors; Biological Markers; Biology; Body mass index; Cancer Biology; Caucasians; Caucasoid Race; Cell Proliferation; Chronic Disease; Clinical; Complex; Data; Diabetes Mellitus; Diagnosis; Disease; Disease Outcome; ERBB2 gene; Environmental Risk Factor; Estrogen Receptors; Ethnic Origin; Ethnic group; Foundations; Frequencies; Gene Expression; Gene Expression Profiling; Genes; Genetic; Gonadal Steroid Hormones; Hawaiian population; Heart Diseases; Hyperinsulinism; IGF1 gene; IGF1R gene; IGF2 gene; IGFBP2 gene; IGFBP3 gene; IL8 gene; Incidence; Individual; Inflammatory; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Insulin-Like Growth Factor Receptor; Insulin-Like Growth-Factor-Binding Proteins; Interleukin-6; Investigation; Japanese Population; Knowledge; Latino; Leptin; Link; Malignant Neoplasms; Mammary Neoplasms; Medical Surveillance; Molecular; Molecular Profiling; National Cancer Institute; Obesity; Outcome; Overweight; Pacific Island Americans; Pathologic; Pathway interactions; Pattern; Population; Predisposition; Prognostic Factor; Proteins; Public Health; Race; Risk; Risk Factors; Role; Sampling; Signal Transduction; Signaling Molecule; Socioeconomic Factors; Socioeconomic Status; Somatomedins; Stage at Diagnosis; Survival Rate; TNF gene; Time; Tissue Microarray; Tissue Sample; Tissues; Treatment Factor; Tumor Tissue; United States; Weight; Woman; Work; base; cancer risk; cohort; cytokine; experience; genome-wide; health disparity; high risk; improved; lifestyle factors; malignant breast neoplasm; modifiable risk; mortality; outcome forecast; population based; prognostic; protein expression; public health relevance; racial and ethnic; racial and ethnic disparities; treatment strategy

DESCRIPTION (provided by applicant): Breast cancer is the most common cancer among women in the U.S. Breast cancer incidence and mortality rates vary across racial/ethnic groups, yet the majority of our biological knowledge about breast cancer is based on Caucasian women. Breast cancer is a complex disease with multiple factors such as environmental, socioeconomic, treatment, and biological factors (including genetics) influencing risk and survival. Therefore it s essential that we initiate studies including individuals from other racial/ethnic groups. Based on data from the National Cancer Institute's Surveillance Epidemiology and End Results (SEER), Native Hawaiian women have the highest breast cancer incidence and mortality rates in the nation. However detailed characterization of breast cancer biology and prognostic factors for Native Hawaiian women has been remarkably limited. Our study focuses on the established link between excess weight and breast cancer in Native Hawaiian women. Studies have shown that overweight/obese women are at greater risk of developing breast cancer and experience poorer outcomes with breast cancer. The role of excess weight for breast cancer can be particularly impactful for Native Hawaiian women because at least 70% of the Native Hawaiian women are overweight/obese. High levels of bioavailable insulin-like growth factors (IGF), as a result of insulin resistance associated with obesity, have been proposed as a candidate mechanism for the increased risk and poor survival of obese women with breast cancer. We intend to characterize the role of IGFs in Native Hawaiian breast cancer with two primary aims. In the first aim we intend to examine the role of obesity and IGF-activation in ER-positive Native Hawaiian breast cancer cases with poor and good overall and breast cancer-specific survival. IGF-pathway activation will be assessed by gene expression profiling of a panel of genes previously established to be up- or down- regulated upon IGF-1 activation. The second aim will compare the association of tissue specific expression of IGF, IGFBP, and IGFR proteins in with breast cancer-specific and overall survival for Native Hawaiian, Asian, and Caucasian women. An established annotated population-based breast cancer tissue microarray will be used to assay protein expression profiles and these profiles will be correlated with breast cancer survival. The proposed work will provide important information regarding the biological mechanisms that impact Native Hawaiian breast cancer and establish a foundation for tailored clinical strategies to target the IGF-pathway for this population.

描述（由申请人提供）：乳腺癌是美国女性中最常见的癌症。乳腺癌的发病率和死亡率因种族/民族而异，但我们关于乳腺癌的大多数生物学知识是基于高加索女性。乳腺癌是一种复杂的疾病，有多种因素，如环境，社会经济，治疗和生物因素（包括遗传学）影响风险和生存。因此，我们必须启动包括其他种族/民族群体的研究。根据国家癌症研究所的监测流行病学和最终结果（SEER）的数据，夏威夷土著妇女的乳腺癌发病率和死亡率在全国最高。然而，夏威夷土著妇女乳腺癌生物学和预后因素的详细特征非常有限。我们的研究重点是夏威夷土著妇女超重和乳腺癌之间的联系。研究表明，超重/肥胖女性患乳腺癌的风险更大，乳腺癌的预后更差。超重对乳腺癌的作用对夏威夷土著妇女特别有影响，因为至少70%的夏威夷土著妇女超重/肥胖。高水平的生物可利用的胰岛素样生长因子（IGF），作为与肥胖相关的胰岛素抵抗的结果，已被提出作为肥胖女性乳腺癌风险增加和生存率差的候选机制。我们打算描述胰岛素样生长因子在夏威夷土著乳腺癌中的作用，主要有两个目的。在第一个目标中，我们打算研究肥胖和IGF激活在ER阳性夏威夷土著乳腺癌病例中的作用，这些病例的总体生存率和乳腺癌特异性生存率较差和较好。将通过先前确定在IGF-1活化后上调或下调的一组基因的基因表达谱分析来评估IGF途径活化。第二个目标是比较组织特异性表达的IGF，IGFBP和IGFR蛋白与乳腺癌特异性和总生存率的夏威夷土著，亚洲和高加索妇女的关联。一个已建立的注释的基于人群的乳腺癌组织微阵列将用于测定蛋白质表达谱，这些谱将与乳腺癌生存相关。拟议的工作将提供有关影响夏威夷原住民乳腺癌的生物学机制的重要信息，并为针对该人群的IGF途径的定制临床策略奠定基础。