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癌症之一，每年导致超过 60,000 例新发病例和 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%)，其中一部分进一步进展为肌肉侵袭性疾病，且生存率较差。由于这种明显高的复发和进展，患者需要接受膀胱镜检查和重复经尿道操作的密集随访，使膀胱癌成为成本最高的疾病之一。十字花科蔬菜的摄入与降低原发性膀胱癌的风险和提高生存率有关，这可能部分归因于其独特的植物化学物质异硫氰酸盐（ITC）。膳食 ITC 是有前途的化学预防剂，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强烈支持膳食 ITC 和富含 ITC 的十字花科蔬菜在预防膀胱癌复发和进展以及改善预后方面发挥着关键作用。最重要的是，通过人体的代谢途径，口服摄入的 ITC 会迅速输送到膀胱并在尿液中浓缩，使膀胱癌成为其抗癌活性的最佳靶标。 本申请要求对 Kaiser Permanente 北加州 (KPNC) 和南加州 (KPSC) 医疗护理计划中的 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以及与 ITC 代谢相关的遗传多态性在潜在减少疾病复发和进展以及提高膀胱内治疗功效方面的作用。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之间的关联； 2）ITC代谢基因多态性对十字花科蔬菜摄入量与膀胱癌复发和进展之间关系的修饰作用； 3）十字花科蔬菜摄入量和治疗药物之间的相互作用对膀胱癌复发和进展的影响。此外，我们建议建立最大的非肌层浸润性膀胱癌患者前瞻性队列，并提供纵向问卷数据和生物样本库，以便进一步研究膀胱癌的结局，包括生存和生活质量。 考虑到膀胱癌的高发病率和复发率、高临床管理成本以及对生活质量的重大影响，膀胱癌是一种研究极少的疾病。拟议的研究是在美国最大的综合医疗机构之一进行的，这将是第一个调查 dit 在疾病复发和进展中的作用的研究，并考虑基因图谱来确定受益最大的人。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产生直接影响。