Diet and Lifestyle in a Prospective Study of Bladder Cancer Survivors

膀胱癌幸存者的饮食和生活方式前瞻性研究

• 批准号: 9059032
• 负责人: LAWRENCE H KUSHI
• 金额: $ 98.7万
• 依托单位: KAISER FOUNDATION RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-02 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9059032
• 关键词: Accounting; Address; Adverse effects; Age; Animal Model; Arsenic; Biological Availability; Bladder; California; Calmette-Guerin Bacillus; Cancer Patient; Cancer Prognosis; Cancer Survivor; Cancer cell line; Caring; Cessation of life; Chemopreventive Agent; Clinical Management; Cohort Studies; Cystoscopy; Databases; Diagnosis; Diet; Diet Modification; Dietary Isothiocyanate; Disease; Disease Progression; Enhancers; Enzymes; Epidemiologic Studies; Epithelial; Epithelium; Ethnic Origin; Future; Genes; Genetic; Genetic Polymorphism; Goals; Health; Healthcare; Human; Immune system; Immunotherapeutic agent; In Vitro; Incidence; Individual; Intake; Intervention Trial; Isothiocyanates; Lamina Propria; Life Style; Long-Term Effects; Malignant Neoplasms; Malignant neoplasm of urinary bladder; Measures; Medical; Metabolic Pathway; Metabolism; Mitomycins; Modality; Muscle; NQO1 gene; Newly Diagnosed; Occupations; Older Population; Outcome; Oxidoreductase; Patients; Phase; Phytochemical; Play; Prevention; Prospective Studies; Public Health; Quality of life; Questionnaires; Quinones; Race; Recurrence; Request for Applications; Retrospective Studies; Risk; Role; Smoking; Staging; Therapeutic Agents; Therapeutic Effect; Time; Treatment Efficacy; United States; Urine; Vegetables; Work; cancer diagnosis; cancer recurrence; cancer risk; cancer survival; chemotherapeutic agent; clinical care; cohort; cooking; cost; cruciferous vegetable; drug sensitivity; genetic profiling; genetic variant; high risk; immune function; improved; in vivo; intravesical; lifestyle factors; outcome forecast; prevent; programs; prospective; sex; tumor; tumor progression; urinary

DESCRIPTION (provided by applicant): Bladder cancer is one of the top ten most common cancers in the U.S., contributing to over 60,000 new cases and 10,000 deaths annually. The majority of cases (70-80%) are diagnosed at early stage (termed "non-muscle invasive"), yet the cancer typically recurs (50-80%), with a subset further progressing to muscle- invasive disease with poor survival. Due to this markedly high recurrence and progression, patients are followed intensively by cystoscopy with repeat transurethral manipulation, making bladder cancer one of the most costly diseases. Cruciferous vegetable intake has been associated with reduced risk of primary bladder cancer and improved survival, which might be partly attributable to their unique phytochemical isothiocyanates (ITCs). Dietary ITCs are promising chemopreventive agents with multi-faceted anti-cancer mechanisms. Our prior in vitro, in vivo, and epidemiologic studies strongly support dietary ITCs and ITC-rich cruciferous vegetables playing a key role in preventing bladder cancer recurrence and progression and improving prognosis. Above all, via metabolic pathways in humans, orally ingested ITCs are rapidly delivered to the bladder and concentrated in the urine, rendering bladder cancer the best target for their anti-cancer activities. This application requests to conduct a new prospective cohort study of 1,811 newly diagnosed non- muscle invasive bladder cancer patients in the Kaiser Permanente Northern California (KPNC) and Southern California (KPSC) Medical Care Programs. Our goal is to comprehensively examine the role of cruciferous vegetable intake, in conjunction with genetic polymorphisms related to ITC metabolism, in potentially reducing disease recurrence and progression, and increasing the efficacy of intravesical treatment. We propose to investigate: 1) the associations between cruciferous vegetable intake and bladder cancer recurrence and progression; 2) the modifying effect of polymorphisms of ITC-metabolizing genes on the associations between cruciferous vegetable intake and bladder cancer recurrence and progression; and 3) the effects of the interactions between cruciferous vegetable intake and therapeutic agents on bladder cancer recurrence and progression. Furthermore, we propose to establish the largest prospective cohort of non-muscle invasive bladder cancer patients with longitudinal questionnaire data and banked biospecimens for further future research of bladder cancer outcomes including survival and quality of life. Bladder cancer is an extremely understudied disease considering its disproportionate high incidence and recurrence, high cost of clinical management, and significant impact on quality of life. The proposed study within one of the largest U.S. integrated health care settings will be the first to investigate the role of dit in recurrence and progression of the disease, with genetic profiles taken into consideration to identify those who will benefit most. Considering the wide availability of cruciferous vegetables in the U.S., this study could have an immediate impact on bladder cancer prognosis.

描述（由申请人提供）：膀胱癌是美国十大最常见的癌症之一，每年导致超过60,000例新病例和10,000例死亡。大多数病例（70-80%）在早期被诊断出来（称为“非肌肉侵袭性”），但癌症通常会复发（50-80%），其中一部分进一步发展为肌肉侵袭性疾病，生存率较低。由于这种明显的高复发和进展，患者经常接受膀胱镜检查和反复经尿道操作，使膀胱癌成为最昂贵的疾病之一。十字花科蔬菜的摄入与原发性膀胱癌的风险降低和生存率提高有关，这可能部分归因于其独特的植物化学异硫氰酸酯（ITCs）。食源性ITCs是一种很有前景的化学预防药物，具有多方面的抗癌机制。我们之前的体外、体内和流行病学研究有力地支持了饮食中的ITCs和富含ITCs的十字花科蔬菜在预防膀胱癌复发、进展和改善预后方面的关键作用。最重要的是，通过人体的代谢途径，口服的ITCs迅速传递到膀胱并浓缩在尿液中，使膀胱癌成为其抗癌活性的最佳靶点。本申请要求对Kaiser Permanente北加州（KPNC）和南加州（KPSC）医疗保健计划中1,811名新诊断的非肌肉浸润性膀胱癌患者进行一项新的前瞻性队列研究。我们的目标是全面研究十字花科蔬菜摄入量与ITC代谢相关的遗传多态性在潜在地减少疾病复发和进展以及提高膀胱内治疗效果方面的作用。我们建议研究：1)十字花科蔬菜摄入量与膀胱癌复发和进展的关系；2) tc代谢基因多态性对十字花科蔬菜摄取量与膀胱癌复发进展相关性的调节作用；3)十字花科蔬菜摄入量与治疗药物相互作用对膀胱癌复发进展的影响。此外，我们建议建立最大的非肌肉浸润性膀胱癌患者的前瞻性队列，包括纵向问卷调查数据和储存的生物标本，以进一步研究膀胱癌的预后，包括生存和生活质量。膀胱癌发病率高、复发率高、临床治疗费用高、对生活质量影响大，是一种研究极为不足的疾病。这项在美国最大的综合医疗机构之一进行的拟议研究将是第一个调查dit在疾病复发和进展中的作用的研究，并将遗传谱考虑在内，以确定哪些人将受益最大。考虑到十字花科蔬菜在美国的广泛供应，这项研究可能对膀胱癌的预后有直接的影响。