Prospective Study of Breast Cancer Survivorship

乳腺癌存活率的前瞻性研究

基本信息

批准号：
7926474
负责人：
LAWRENCE H KUSHI
金额：
$ 94.54万
依托单位：
KAISER FOUNDATION RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-15 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7926474
关键词：
Aberrant DNA Methylation Address Affect Antioxidants Ascorbic Acid BRCA1 gene Biological Factors Blood specimen CDH1 gene CDKN2A gene CYP3A4 gene Cadherins California Cancer Prognosis Cancer Survivorship Cells Cessation of life Characteristics Cohort Studies Complementary and alternative medicine Complex Cyclophosphamide DAP kinase DNA DNA Methylation DNA Repair Data Databases Diagnosis Diet Dietary Factors Disease-Free Survival E-Cadherin ERCC1 gene Effectiveness Enrollment Erythrocytes Estrogen Receptor Status Estrogens Fatty acid glycerol esters Folate Folic Acid Food Frequencies Funding Future GSTM1 gene GSTP1 gene GSTT1 gene Gene Expression Genes Genetic Genetic Polymorphism Histologic Histopathologic Grade Hour Individual Inherited Intake Interview Investigation Knowledge LIG4 gene Life Style Macronutrients Nutrition Malignant Neoplasms Mammary Neoplasms Medical Metabolic Metabolism Methylation Molecular Mutation Nutrient Other Genetics Participant Pathology Report Pathway interactions Patients Phase Physical activity Phytoestrogens Plasma Play Prevalence Prognostic Factor Prospective Studies Quality of life Questionnaires Radiation Radiation therapy Reactive Oxygen Species Recurrence Relative (related person)Relative Risks Research Resources Risk Risk Factors Role S-Phase Fraction Specimen TP53 gene Tamoxifen Therapeutic Therapeutic Agents Treatment Efficacy Treatment Protocols Woman Work XRCC1 gene XRCC3 gene breast cancer diagnosis cancer recurrence cell killing chemotherapeutic agent chemotherapy computerized conventional therapy cytotoxic enzyme activity fruits and vegetables glypican 3 hazard human APEX1 protein improved interest lifestyle factors malignant breast neoplasm molecular marker mortality neoplastic cell outcome forecast overexpression oxidative damage prospective soy tumor

项目摘要

DESCRIPTION (provided by applicant): Despite substantial lifestyle changes such as in diet or use of complementary and alternative medicine (CAM) among women with breast cancer, few studies have examined whether such factors improve prognosis. These factors may also influence quality of life, which may in turn influence prognosis. How these factors influence prognosis may depend in part on molecular characteristics such as genetic polymorphisms that influence oxidative damage or DNA repair, or aberrant DNA methylation which influences gene expression. These markers may themselves influence prognosis or interact with conventional therapies. We propose to address these gaps in knowledge by establishing the largest prospective cohort study of women with breast cancer to date. We will enroll at least 5,021 women with breast cancer from Kaiser Permanente of Northern California (KPNC). With extremely rapid case ascertainment through computerized pathology reports, we can identify cases of breast cancer as they are confirmed histologically, minimizing survival bias. We will interview and send questionnaires to participants, and extract data from medical charts and KPNC databases. Blood samples will be collected prior to treatment to characterize genetic polymorphisms, and tumor specimens will be obtained to examine aberrant DNA methylation. Blood samples and breast tumor DNAs will also be banked for future use. This resource will enable study of the effects on recurrence and survival of: 1) lifestyle factors, including diet, physical activity, use of CAM, and quality of life; and, 2) host and tumor molecular characteristics, including genetic polymorphisms (e.g., those involved in: cyclophosphamide (CYP3A4, GSTP1, GSTA1) or tamoxifen metabolism (SULTIA1); protection against oxidative damage (MnSOD, CAT, GPX1, GSTM1, GSTT1); and DNA repair (XRCC1, LIG4, XRCC3, XPD, ERCC1, APE1)), and aberrant DNA methylation of genes in breast tumors (BRCA1, P161NK4a, E-Cadherin, glypican3, DUTT1, HIC1, TSLC1, DAP-kinase, GSTP1). Using proportional hazards regression, we will examine associations of lifestyle factors and molecular markers on risk of recurrence and mortality; we estimate at least 599 recurrences and 331 deaths during the 5-year funding period. For survival, we will have power to detect a relative hazard of 1.64 comparing upper to lower quartiles of continuous exposures such as nutrient intake, and a relative hazard of 159 for an exposure with prevalence of 0.10. This study will provide some of the first information on these risk factors and breast cancer prognosis.

描述（由申请人提供）：尽管乳腺癌女性的生活方式发生了重大变化，例如饮食或使用补充和替代医学（CAM），但很少有研究探讨这些因素是否可以改善预后。这些因素也可能影响生活质量，进而影响预后。这些因素如何影响预后可能部分取决于分子特征，例如影响氧化损伤或 DNA 修复的遗传多态性，或影响基因表达的异常 DNA 甲基化。这些标志物本身可能影响预后或与常规疗法相互作用。我们建议通过建立迄今为止最大的乳腺癌女性前瞻性队列研究来解决这些知识差距。我们将从北加州 Kaiser Permanente (KPNC) 招募至少 5,021 名患有乳腺癌的女性。通过计算机化病理报告极其快速地确定病例，我们可以识别经过组织学证实的乳腺癌病例，从而最大限度地减少生存偏差。我们将对参与者进行访谈并向其发送调查问卷，并从医疗图表和 KPNC 数据库中提取数据。治疗前将采集血样以表征遗传多态性，并获取肿瘤标本以检查异常 DNA 甲基化。血液样本和乳腺肿瘤 DNA 也将被储存以供将来使用。该资源将有助于研究以下因素对复发和生存的影响：1) 生活方式因素，包括饮食、体力活动、CAM 的使用和生活质量； 2) 宿主和肿瘤分子特征，包括遗传多态性（例如，参与环磷酰胺（CYP3A4、GSTP1、GSTA1）或他莫昔芬代谢（SULTIA1）的多态性；防止氧化损伤（MnSOD、CAT、GPX1、GSTM1、GSTT1） ; 和 DNA 修复（XRCC1、LIG4、XRCC3、XPD、ERCC1、 APE1))，以及乳腺肿瘤中基因的异常 DNA 甲基化（BRCA1、P161NK4a、E-钙粘蛋白、磷脂酰肌醇蛋白聚糖 3、DUTT1、HIC1、TSLC1、DAP 激酶、GSTP1）。使用比例风险回归，我们将检查生活方式因素和分子标记物与复发和死亡风险的关联；我们估计在 5 年资助期内至少有 599 例复发和 331 例死亡。为了生存，我们将有能力比较连续暴露（例如营养摄入）的上四分位数和下四分位数，检测到相对风险为 1.64，对于流行率为 0.10 的暴露，我们将有能力检测到相对风险为 159。这项研究将提供有关这些危险因素和乳腺癌预后的一些初步信息。