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Abstract：
METHODS: 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.
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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
方法：饮食中异硫氰酸盐（ITC）暴露于十字花科蔬菜（CV）摄入可能会改善非肌层浸润性膀胱癌（NMIBC）的预后。这项研究旨在调查关键ITC代谢/功能基因的遗传变异是否会改变饮食ITC暴露与NMIBC预后结果之间的关联。
结果：在膀胱癌流行病学中，健康，和生活方式研究（Be-WellStudy），1472例NMIBC患者的前瞻性队列，通过自我报告的CV摄入量评估膳食ITC暴露,并在血浆ITC-白蛋白加合物中测量。使用Cox比例风险回归模型，通过9个关键ITC代谢/功能基因的单核苷酸多态性（SNP）分层，计算复发和进展的风险比(HR)和95%置信区间(CIs).N-乙酰转移酶1（NAT1）中的rs15561改变了CV摄入与进展风险之间的关联。核因子E2相关因子2（NRF2）和核因子κB（NFκB）中的多个SNP修饰了血浆ITC-白蛋白加合物水平与进展风险之间的关联（pint<0.05）。没有观察到与复发风险的显著关联。总的来说,>80％的研究参与者每个基因至少有一个保护性基因型，显示高膳食ITC暴露的进展风险平均降低65%。
结论：尽管ITC代谢/功能基因的遗传变异可能会改变膳食ITC对NMIBC预后的影响，饮食建议食用CV可能有助于提高NMIBC的生存率。
结果：在膀胱癌流行病学中，健康，和生活方式研究（Be-WellStudy），1472例NMIBC患者的前瞻性队列，通过自我报告的CV摄入量评估膳食ITC暴露,并在血浆ITC-白蛋白加合物中测量。使用Cox比例风险回归模型，通过9个关键ITC代谢/功能基因的单核苷酸多态性（SNP）分层，计算复发和进展的风险比(HR)和95%置信区间(CIs).N-乙酰转移酶1（NAT1）中的rs15561改变了CV摄入与进展风险之间的关联。核因子E2相关因子2（NRF2）和核因子κB（NFκB）中的多个SNP修饰了血浆ITC-白蛋白加合物水平与进展风险之间的关联（pint<0.05）。没有观察到与复发风险的显著关联。总的来说,>80％的研究参与者每个基因至少有一个保护性基因型，显示高膳食ITC暴露的进展风险平均降低65%。
结论：尽管ITC代谢/功能基因的遗传变异可能会改变膳食ITC对NMIBC预后的影响，饮食建议食用CV可能有助于提高NMIBC的生存率。
