Prospective Study of Breast Cancer Survivorship

乳腺癌存活率的前瞻性研究

• 批准号: 7119479
• 负责人: LAWRENCE H KUSHI
• 金额: $ 201.28万
• 依托单位: KAISER FOUNDATION RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-20 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7119479
• 关键词: alternative medicine; biomarker; breast neoplasms; cancer registry /resource; clinical research; female; genetic polymorphism; genetic susceptibility; human genetic material tag; human subject; lifestyle; long term survivor; longitudinal human study; neoplasm /cancer epidemiology; neoplasm /cancer genetics; neoplasm /cancer relapse /recurrence; nucleic acid methylation; nutrition aspect of cancer; nutrition related tag; outcomes research; oxidative stress; prognosis; women' s health

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）：尽管乳腺癌妇女的生活方式发生了实质性的改变，如饮食或使用补充和替代医学（CAM），但很少有研究检查这些因素是否能改善预后。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，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治疗相互作用。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空白。