Prospective Study of Breast Cancer Survivorship

乳腺癌存活率的前瞻性研究

• 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
• 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

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）：尽管生活方式发生了很大的变化，例如在乳腺癌女性中进行饮食或互补和替代医学（CAM）的使用，但很少有研究研究这些因素是否改善了预后。这些因素也可能影响生活质量，这可能会影响预后。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。这些标记本身可能会影响预后或与常规疗法相互作用。我们建议通过建立对迄今为止乳腺癌女性的最大前瞻性队列研究来解决这些知识的差距。 我们将至少从北加州Kaiser Permanente（KPNC）入学至少5,021名乳腺癌女性。通过通过计算机病理学报告进行非常快速的病例确定，我们可以在组织学上确认乳腺癌病例，从而最大程度地减少生存偏见。我们将采访并将问卷发送给参与者，并从医疗图表和KPNC数据库中提取数据。将在治疗前收集血样，以表征遗传多态性，并将获得肿瘤标本以检查异常的DNA甲基化。血液样本和乳腺肿瘤DNA也将用于将来使用。 该资源将能够研究以下方面对复发和生存的影响：1）生活方式因素，包括饮食，体育锻炼，使用CAM和生活质量； 2）宿主和肿瘤分子特征，包括遗传多态性（例如，涉及：环磷酰胺（CYP3A4，GSTP1，GSTA1）或他莫昔芬代谢（SULTIA1）（SULTIA1）；保护氧化损害（MNSOD，CAT，CAT，GPX1，GPX1，GPX1，GSTM1，GSTM1，GST1，xtna）； XRCC3，XPD，ERCC1，APE1）和乳腺肿瘤中基因的异常DNA甲基化（BRCA1，P161NK4A，E-CADHERIN，GLYPICAN3，DUTT1，HIC1，HIC1，TSLC1，TSLC1，TSLC1，TSLC1，DAP-KIMIKASE，GSTP1）。 使用比例危害回归，我们将研究生活方式因素和分子标记的关联，均与复发和死亡的风险有关；我们在5年的资金期间估计至少有599例复发和331例死亡。为了生存，我们将有能力检测1.64的相对危害，比较连续暴露（如营养摄入量）的上四分位数，而相对危害为159，以暴露率为0.10。这项研究将提供有关这些危险因素和乳腺癌预后的一些第一个信息。