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

Abstract

ScopeDietary 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 resultsIn 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.ConclusionDespite 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.