# Project 4 - Oral Cell DNA Adducts and Urinary Biomarkers to Investigate Ethnic/Racial Differences in Lung Cancer Susceptibility

> **NIH NIH P01** · UNIVERSITY OF MINNESOTA · 2020 · $195,807

## Abstract

Project 4. Oral Cell DNA Adducts and Urinary Biomarkers to Investigate Ethnic/Racial Differences in 
Lung Cancer Susceptibility. 
ABSTRACT 
Our ongoing studies demonstrate that carcinogen and toxicant doses account for some of the ethnic 
differences in risk for lung cancer among smokers as observed in the Multiethnic Cohort. Carcinogen and 
toxicant dose are only the first part of the risk paradigm for smoking-related lung cancer. DNA adduct formation 
is the next critical step because DNA adducts lead to the multiple mutations that are found in smokers' lungs 
and that cause miscoding, genetic instability, and cancer. Therefore, in this study, we will compare DNA adduct 
formation in smokers from three ethnic groups with differing risks for lung cancer: Native Hawaiians (highest 
risk), Whites (lower risk), and Japanese Americans (lowest risk). Three-hundred subjects will be recruited by 
the Clinical and Biomarker Core. Oral cells, as a surrogate for lung cells, will be obtained for DNA adduct 
measurements; urine samples will be collected for analysis of carcinogen and toxicant metabolites. Specific 
DNA adducts as well as DNA adductomic signatures will be obtained from oral cells of each subject. Analysis 
of the urine samples as well as those previously collected from never smokers will test the hypothesis that the 
high lung cancer susceptibility of Native Hawaiians is partially due to endogenous generation of the toxicants 
acrolein and crotonaldehyde, possibly due to inflammation and oxidative damage. Thus, our specific aims are: 
1. Using high resolution mass spectrometry, quantify known DNA adducts in oral mucosa cells of 100 
 smokers from each ethnic group – Native Hawaiians, Whites, and Japanese Americans. DNA adducts of 
 tobacco-specific compounds, formaldehyde, and acrolein will be quantified. 
2. Analyze the urine of 100 smokers and 100 non-smokers from each of these groups for mercapturic acids of 
 acrolein and crotonaldehyde, the F2-isoprostane 8-iso-PGF-2α, a biomarker of oxidative damage, and the 
 prostaglandin E2 metabolite PGEM, a biomarker of inflammation, as well as total nicotine equivalents and 
 total NNAL (smokers only). These data will provide critical information relevant to the high risk of Native 
 Hawaiians for lung cancer, and in relationship to the DNA adduct measurements of Specific Aim 1. 
3. Use our newly developed high resolution mass spectrometric, high throughput DNA adductomic approach 
 to screen for known and unknown DNA adducts to identify a comprehensive DNA modification signature 
 derived from cigarette smoking. 
a. Using a targeted DNA adductomic method we will screen for multiple DNA modifications 
 simultaneously. The adducts analyzed in Specific Aim 1 will be added to a list including 
 endogenous, 1,3-butadiene-derived (in collaboration with Project 3), aldehyde-derived and 
 nitrosamine or alkylating agent-derived DNA adducts. In parallel we will apply our DNA adductomic 
 method in an unt...

## Key facts

- **NIH application ID:** 9994214
- **Project number:** 5P01CA138338-10
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** STEPHEN S HECHT
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $195,807
- **Award type:** 5
- **Project period:** — → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994214

## Citation

> US National Institutes of Health, RePORTER application 9994214, Project 4 - Oral Cell DNA Adducts and Urinary Biomarkers to Investigate Ethnic/Racial Differences in Lung Cancer Susceptibility (5P01CA138338-10). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9994214. Licensed CC0.

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