Associations of dietary isothiocyanate exposure from cruciferous vegetable consumption with recurrence and progression of non–muscle-invasive bladder cancer: findings from the Be-Well Study

• Published in: The American journal of clinical nutrition Vol. 117; no. 6; pp. 1110 - 1120
• Main Authors: Wang, Zinian, Kwan, Marilyn L., Haque, Reina, Goniewicz, Maciej, Pratt, Rachel, Lee, Valerie S., Roh, Janise M., Ergas, Isaac J., Cannavale, Kimberly L., Loo, Ronald K., Aaronson, David S., Quesenberry, Charles P., Zhang, Yuesheng, Ambrosone, Christine B., Kushi, Lawrence H., Tang, Li
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-06-2023; American Society for Clinical Nutrition, Inc; American Society for Nutrition
• Subjects: Adducts; Albumin; Albumins; Anticancer properties; biomarker; Bladder; Bladder cancer; Brassicaceae; cruciferous vegetable; Diet; Dietary intake; Exposure; Health hazards; Humans; Invasiveness; isothiocyanate; Isothiocyanates - pharmacology; Metabolites; Muscles; Neoplasm Recurrence, Local; Non-Muscle Invasive Bladder Neoplasms; non–muscle-invasive bladder cancer; Original; Prognosis; progression; Prospective Studies; recurrence; Regression analysis; Regression models; Risk management; Statistical analysis; Urinary Bladder Neoplasms - prevention & control; Vegetables; BC; isothiocyanate; NMIBC; TURBT; non–muscle-invasive bladder cancer; progression; HR; EHR; FFQ; Nrf2-ARE; KPSC; cruciferous vegetable; BMI; OR; PEITC; CI; BCG; Be-Well Study; BITC; biomarker; recurrence; CV; ITC; KPNC; MIBC; Tis
• ISSN: 0002-9165; 1938-3207; 1938-3207
• DOI: 10.1016/j.ajcnut.2023.04.006

High recurrence and progression rates are major clinical challenges for non–muscle-invasive bladder cancer (NMIBC). Dietary isothiocyanates (ITCs), phytochemicals primarily from cruciferous vegetables (CV), show strong anticancer activities in preclinical BC models, yet their effect on NMIBC prognosis remains unknown.
This study aimed to investigate the associations of dietary ITC exposure at diagnosis with NMIBC recurrence and progression.
The study analyzed 1143 participants from the Be-Well study, a prospective cohort of newly diagnosed NMIBC cases in 2015–2019 with no prior history of BC. Dietary ITC exposure was indicated by self-reported CV intake, estimated ITC intake, urinary metabolites, and plasma ITC–albumin adducts. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrence and progression, and unconditional logistic regression models were used to calculate odds ratios (ORs) and 95% CIs for delayed and multiple recurrence.
Over a mean follow-up of 25 mo, 347 (30%) developed recurrence and 77 (6.7%) had disease progression. Despite no significant associations with the overall risk of recurrence, urinary ITC metabolites (OR: 1.96; 95% CI: 1.01, 4.43) and dietary ITC intake (OR: 2.13; 95% CI: 1.03, 4.50) were associated with late recurrence after 12-mo postdiagnosis compared with before 12-mo postdiagnosis. Raw CV intake was associated with reduced odds of having ≥2 recurrences compared with having one (OR: 0.34; 95% CI: 0.16, 0.68). Higher plasma concentrations of ITC–albumin adducts were associated with a reduced risk of progression, including progression to muscle-invasive disease (for benzyl ITC, HR: 0.40; 95% CI: 0.17, 0.93; for phenethyl ITC, HR: 0.40; 95% CI: 0.19, 0.86).
Our findings indicate the possible beneficial role of dietary ITCs in NMIBC prognosis. Given the compelling preclinical evidence, increasing dietary ITC exposure with CV intake could be a promising strategy to attenuate recurrence and progression risks in patients with NMIBC.