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.
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