# Identify the DNA Adduct and Associated  Metabolic Alterations in Bladder Cancer  of Smokers

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2020 · $391,127

## Abstract

Project Summary/Abstract
Smoking is a major risk factor for bladder cancer (BCa). Patients with current or past history of smoking have a
three times higher likelihood of developing BCa. Smoking is also known to have a potential dose-dependent
effect on the grade and stage of BCa, with high-dose smokers having more aggressive disease. In addition,
smokers with BCa have a higher likelihood of failing chemotherapy. Currently, markers that can stratify
smokers based on their risk of developing BCa are lacking. Furthermore, predictive markers for aggressive
BCa among high-dose smokers are also lacking. The central goal of this application is to characterize the
DNA adducts and biochemical alterations observed in smoking-associated BCa and use this information to
develop metabolite-based predictive markers and therapeutic strategies for this deadly disease. Cigarette
smoke contains a number of xenobiotic compounds that include arylamines, methylated metabolites, Nicotine-
derived nitrosamine ketone (NNK), Benzo[a]pyrene (BaP), nicotine etc which are usually metabolized by the
xenobiotic metabolism and excreted in the urine. Our strong preliminary data demonstrates altered DNA
adducts and reprogramming of xenobiotic metabolism in BCa smokers. This effect is exaggerated by
components of cigarette smoke including nicotine. Using a novel metabolomics approach, we had earlier
shown that BCa was associated with a unique metabolic signature. From the patients perspective it is
important to be able to measure these markers non-invasively in body fluids like urine. Intriguingly, metabolites
are the end products of overall cellular metabolism. These are small molecules that could be easily monitored
in body fluids to interrogate disease phenotype in question. Quiet provocatively, our group is being established
to utilize metabolites to further monitor tumors. Thus, our current proposal aims to identify DNA adducts and
associated metabolites in BCa smokers and use the information to develop markers for early identification of
patients who are at risk for developing aggressive bladder cancer. Further will enable clinicians to take an
informed decision about more appropriate therapeutic strategies towards personalized medicine.

## Key facts

- **NIH application ID:** 9895423
- **Project number:** 5R01CA216426-03
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** RANDA A EL-ZEIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $391,127
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9895423

## Citation

> US National Institutes of Health, RePORTER application 9895423, Identify the DNA Adduct and Associated  Metabolic Alterations in Bladder Cancer  of Smokers (5R01CA216426-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9895423. Licensed CC0.

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