Stem cells and perinatal factors for breast cancer risk

干细胞和围产期因素对乳腺癌风险的影响

• 批准号: 7647168
• 负责人: CHUNG-CHENG HSIEH
• 金额: $ 38.55万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-15 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7647168
• 关键词: Address; Adult; Angiogenic Factor; Biological; Birth Weight; Blood specimen; Breast; Breast Cancer Risk Factor; CD34 gene; Cancer Patient; Cell Count; Cells; Characteristics; Child; Diagnosis; Early identification; Endothelial Cells; Environment; Epidemiologic Studies; Estradiol; Estriol; Event; Fetal Growth Retardation; Functional disorder; Funding; Future; Goals; Grant; Growth Factor; Hematopoietic stem cells; Hormonal; Hormonal Carcinogenesis; Hormones; Human; Individual; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Lead; Life; Link; Malignant Neoplasms; Measurement; Measures; Neonatal; Newborn Infant; Outcome; Participant; Patients; Perinatal; Perinatal Exposure; Pre-Eclampsia; Predisposition; Premature Birth; Process; Progesterone; Prolactin; Proliferating; Prophylactic treatment; Proteins; Regression Analysis; Relative (related person); Risk; Risk Factors; Sex Hormone-Binding Globulin; Stem cells; Testosterone; Tissue Sample; Tissues; Tumor Tissue; Twin Multiple Birth; Umbilical Cord Blood; angiogenesis; base; breast cancer diagnosis; cancer prevention; cancer risk; cancer stem cell; carcinogenesis; cell growth; high risk; hormone related cancer; in utero; indexing; interest; malignant breast neoplasm; non-genetic; novel; offspring; peripheral blood; prenatal; public health relevance

DESCRIPTION (provided by applicant): The goal of CA90902 is to examine in umbilical cord blood samples the relation between measurements of stem cell potential and perinatal factors for breast cancer risk. The study is based on the hypothesis that cancer risk can be influenced in part by the hormonal environment in utero and that cancer risk is proportional to the number of primitive proliferating stem cells. In the previous grant cycle, we focused on the correlations between standard hematopoietic stem cell measurements and major endogenous hormones as well as birth weight. Building on the emerging results, we propose in this continuation application to explore further the relation between stem cell measurements and additional perinatal characteristics (preeclampsia, twin membership, and preterm birth) and endogenous hormones and growth factors (IGF-2) that have been found to be associated with breast cancer risk in adult life in epidemiologic studies or that might be relevant in prenatal origin hypothesis on breast cancer risk. Stem cell and growth factor measurements expand to include endothelial progenitor cells and angiogenic factors that might be related to intrauterine growth retardation. Umbilical cord blood from 240 donors with a wide range of maternal, gestational, and neonatal characteristics will be included. Stem cells include CD34+, CD34+/CD38-, CD34+/CD133+/VEGFR-2+ subpopulations, as well as colony-forming cells will be measured. Pro- and anti-angiogenic factors will be measured to assess angiogenic potential and to correlate with levels of endothelial progenitor cells and other study variables. We will apply regression analysis treating as outcome variables each measurement of stem cell potential and as predictor variables perinatal characteristics, hormones, and angiogenic factors. A third aim will examine whether patients diagnosed with breast cancer (n=80) have higher measurements of stem cell potential than control subjects without breast cancer (n=80). It will also explore whether levels of hematopoietic stem cells in the breast cancer patients are correlated with CD44+/CD24- cells, a putative breast cancer stem cell, in their tumor tissue samples. The proposed study could contribute information on whether hormonal carcinogenesis process starts already early in the perinatal period and whether stem cell potential may be a common denominator for the effect of perinatal factors, providing a closer link between in utero exposure and risk of breast and other cancers. More speculatively, examining perinatal factors that include endogenous hormones and maternal, gestational, and neonatal characteristics might also potentially lead to future applications for early identification of high-risk individuals, perhaps through stem cell measurement, for potential cancer prevention measures. PUBLIC HEALTH RELEVANCE: Epidemiologic studies have provided evidence that in utero and perinatal events or conditions impact risk of breast and perhaps other cancers in the offspring. It has been difficult to directly study the pathogenic mechanisms involved in the sequences of events between early life exposures and adult life outcome. The proposed study could contribute information on whether the hormonal-influenced carcinogenesis process starts early in the perinatal period and whether stem cell potential may be viewed as a non-genetic indicator of host susceptibility, summarizing the effects of perinatal factors, and providing a closer link between in utero exposure and breast cancer risk. Examining perinatal risk factors that include endogenous hormones and maternal, gestational, and newborn characteristics might also potentially lead to future applications for early identification of high-risk individuals, through measurement of stem cell potential as a susceptibility marker summarizing the effect of a multitude of factors, for potential cancer surveillance and prevention measures.

描述（由申请人提供）：CA90902的目的是在脐带血样本中检查干细胞潜力的测量与乳腺癌风险的围产因子之间的关系。该研究基于以下假设：癌症的风险可能部分受子宫内激素环境的影响，并且癌症风险与原始增殖干细胞的数量成正比。在上一个赠款周期中，我们专注于标准造血干细胞测量与主要内源激素以及出生体重之间的相关性。在新兴结果的基础上，我们建议在这种持续应用中提出，以进一步探索干细胞测量与其他周围特征（前宾夕法尼亚，双胞胎成员资格和早产）以及内源性激素和生长因子（IGF-2）之间的关系，这些因素和生长因子（IGF-2）与乳腺癌在乳腺癌中的乳腺癌风险相关或可能与PREN癌症相关。干细胞和生长因子的测量扩展为包括内皮祖细胞和可能与宫内生长迟滞有关的血管生成因子。将包括来自240名捐赠者的脐带血，这些供体将包括各种母体，妊娠和新生儿特征。干细胞包括CD34+，CD34+/CD38-，CD34+/CD133+/VEGFR-2+亚群以及菌落形成细胞。将测量促抗血管生成因子，以评估血管生成潜力并与内皮祖细胞和其他研究变量相关。我们将应用回归分析，将干细胞电位的每个测量和预测变量围产期特征，激素和血管生成因子视为结果变量。第三个目标将检查被诊断出患有乳腺癌的患者（n = 80）是否比没有乳腺癌的对照受试者具有更高的干细胞潜力测量值（n = 80）。它还将探索乳腺癌患者中造血干细胞的水平是否与其肿瘤组织样品中假定的乳腺癌干细胞CD44+/CD24-细胞相关。拟议的研究可以贡献有关激素致癌过程是否已经开始在围产期开始的早期开始，以及干细胞电位是否可能是围产期因素作用的共同点，从而在子宫内暴露与乳房风险与乳腺癌和其他癌症的风险之间有更紧密的联系。更具猜测的是，检查包括内源激素以及母体，孕育和新生儿特征在内的围产期因素也可能会导致未来的应用，以便早期鉴定高危人群，也许是通过干细胞测量来进行潜在的预防癌症预防测量。公共卫生相关性：流行病学研究提供了证据，表明在子宫内和围产期事件中，或条件会影响乳房以及后代其他癌症的风险。很难直接研究早期生活暴露与成人生活结果之间事件序列中涉及的致病机制。拟议的研究可以贡献有关激素影响的癌变过程是否在围产期开始开始的信息，以及是否可以将干细胞电位视为宿主易感性的非遗传指标，总结围产期因素的影响，并在子宫癌暴露与乳腺癌的风险中提供更紧密的联系。检查包括内源激素以及母体，妊娠和新生儿特征在内的围产期危险因素，还可能导致未来的应用，通过测量干细胞电位作为易感标志物，总结了众多因素的效果，用于众多因素的效果，用于潜在的癌症监测和预防措施。