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Grant Abstract: Diet and Lifestyle in a Prospective Study of Bladder Cancer Survivors

Grant Number: 5R01CA172855-05
PI Name: Kwan
Project Title: Diet and Lifestyle in a Prospective Study of Bladder Cancer Survivors

Abstract: In response to FOA PA-17-307, Administrative Supplements for Research on Dietary Supplements, this application requests support to the ongoing R01 project (R01CA172855) entitled “Diet and lifestyle in a prospective study of bladder cancer survivors”. The primary goal of the parent study is to comprehensively examine the potential beneficial role of cruciferous vegetable intake, more specifically exposure to their unique phytochemical isothiocyanates (ITCs), in bladder cancer recurrence and progression in a prospective cohort of newly diagnosed patients with non-muscle invasive bladder cancer. ITC exposure is estimated based on cruciferous vegetable intake queried by food frequency questionnaire (FFQ), as well as urinary levels of ITC metabolites. However, FFQ is subjected to recall bias, and urinary ITC levels represent a recent and short-term estimate for cruciferous vegetable intake and/or ITC exposure. In this supplement application, we propose to add measurement of ITC-albumin adducts in human plasma samples as a biomarker for evaluating the role of dietary ITC intake in bladder cancer. There are three advantages of using ITC-albumin adducts as biomarkers for dietary ITC exposure: 1) ITC-albumin adducts present long-term and cumulative exposure to dietary ITCs; 2) ITC-albumin adducts represent biologically relevant exposure at the cellular level; 3) ITC-albumin adducts can provide estimates for ITC-specific exposure and help evaluate the role of individual ITCs. Leveraging the plasma samples collected in the parent study, plasma levels of ITC-albumin adducts will be measured using liquid chromatography-mass spectrometry (LC-MS/MS). The albumin-adduct levels of total and individual ITCs will be compared with dietary ITC intake estimated from FFQ as well as urinary levels of ITC metabolites. Subsequently, the levels of ITC-albumin adducts will be incorporated into all three specific aims proposed in the parent study. Kumar and Sabbioni first proposed in 2010 to examine ITC-albumin adducts as biomarkers for cruciferous vegetable intake using LC-MS/MS, and the method has been tested in a small group of healthy volunteers. The results obtained from this supplemental grant will significantly strengthen and enhance the primary goal of the parent study to understand the role of cruciferous vegetable/ITCs in bladder cancer recurrence and progression. Importantly, the proposed study will provide first-hand data on the applicability and feasibility of using ITC-albumin adducts as biomarkers for dietary ITC exposure in large-scale epidemiological studies.

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