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.

Public Health Relevance

Bladder cancer is one of the top ten cancers diagnosed in the U.S. today, and one of the most expensive to treat due to its extraordinarily high rate of recurrence. Therefore, identification of effective dietary modifications to prevent or delay recurrence and progression of non-muscle invasive bladder cancer, which represents the majority of diagnosed cases, is of great public health importance. We propose to conduct a new prospective cohort of over 1,800 non-muscle invasive bladder cancer cases to investigate the role of cruciferous vegetable intake, along with associated individual genetic profiles, on reducing recurrence and progression of disease and improving the efficacy of current treatment modalities.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
1R01CA172855-01A1
Application #
8695166
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Elena, Joanne W
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Kaiser Foundation Research Institute
Department
Type
DUNS #
City
Oakland
State
CA
Country
United States
Zip Code
94612