Modifying Effects of Genetic Variations on the Association Between Dietary Isothiocyanate Exposure and Non-muscle Invasive Bladder Cancer Prognosis in the Be-Well Study

Mol Nutr Food Res. 2024 Apr;68(8):e2400087. doi: 10.1002/mnfr.202400087. Epub 2024 Apr 6.


Scope: Dietary isothiocyanate (ITC) exposure from cruciferous vegetable (CV) intake may improve non-muscle invasive bladder cancer (NMIBC) prognosis. This study aims to investigate whether genetic variations in key ITC-metabolizing/functioning genes modify the associations between dietary ITC exposure and NMIBC prognosis outcomes.

Methods and results: In the Bladder Cancer Epidemiology, Wellness, and Lifestyle Study (Be-Well Study), a prospective cohort of 1472 incident NMIBC patients, dietary ITC exposure is assessed by self-reported CV intake and measured in plasma ITC-albumin adducts. Using Cox proportional hazards regression models, stratified by single nucleotide polymorphisms (SNPs) in nine key ITC-metabolizing/functioning genes, it is calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrence and progression. The rs15561 in N-acetyltransferase 1 (NAT1) is alter the association between CV intake and progression risk. Multiple SNPs in nuclear factor E2-related factor 2 (NRF2) and nuclear factor kappa B (NFκB) are modify the associations between plasma ITC-albumin adduct level and progression risk (pint < 0.05). No significant association is observed with recurrence risk. Overall, >80% study participants are present with at least one protective genotype per gene, showing an average 65% reduction in progression risk with high dietary ITC exposure.

Conclusion: Despite that genetic variations in ITC-metabolizing/functioning genes may modify the effect of dietary ITCs on NMIBC prognosis, dietary recommendation of CV consumption may help improve NMIBC survivorship.

Keywords: cruciferous vegetables; isothiocyanate; non‐muscle invasive bladder cancer; progression; recurrence; single nucleotide polymorphisms.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Arylamine N-Acetyltransferase / genetics
  • Diet*
  • Female
  • Humans
  • Isothiocyanates* / administration & dosage
  • Isothiocyanates* / pharmacology
  • Male
  • Middle Aged
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Non-Muscle Invasive Bladder Neoplasms
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Prospective Studies
  • Urinary Bladder Neoplasms* / genetics
  • Urinary Bladder Neoplasms* / pathology


  • Isothiocyanates
  • NF-E2-Related Factor 2
  • Arylamine N-Acetyltransferase
  • NFE2L2 protein, human