# Untargeted Adductomics to Characterize Ethnic Differences in the Exposome of Smokers

> **NIH NIH P01** · UNIVERSITY OF MINNESOTA · 2022 · $348,260

## Abstract

ABSTRACT
About 11-24% of smokers will develop lung tumors over their lifetime, with a greater cancer incidence in
African American and Native Hawaiian cigarette smokers as compared with Whites, Japanese Americans, and
Latinos. These differences persist even after adjusting for smoking amounts. Cigarette smoke is a complex
mixture of chemicals including at least 70 known carcinogens, procarcinogens, and inflammatory agents.
Smokers belonging to different ethnic groups may have variable responses towards cigarette smoke due to
inherent genetic and epigenetic differences and ethnicity-related lifestyle factors such as diet, exercise, alcohol
consumption, and environmental exposures. These factors can lead to differing amounts of DNA and protein
adducts in smokers, mediating their sensitivity to smoking-induced mutations and cancer. Recent development
in analytical methodologies and bioinformatics have made it possible to characterize the totality of human
exposures from both external and internal sources (the exposome) using untargeted or multifaceted analyses
of hemoglobin adducts. Hemoglobin is the most abundant protein in human blood with a relatively long half-life,
and hemoglobin adducts reflect cumulative exposures to electrophiles. The adductomics approach is
analogous to other -omics methodologies such as genomics, transcriptomics, and metabolomics, which are
making it possible to understand and view complex human diseases such as cancer from a global perspective.
Adductomics studies in smokers will capture individual physiological responses to smoking, potentially
uncovering new factors that contribute to lung cancer risk.
We hypothesize that due to genetic differences and ethnic variations in diet, lifestyle, and environmental
exposures, human populations of different ethnicity/race form variable numbers of protein and DNA adducts,
which contributes to ethnic disparities in lung cancer risk following exposure to tobacco smoke. The objective
of this application is to characterize the exposomes of smokers, former smokers, and never smokers, to
investigate inter-individual and inter-ethnic/racial differences in formation of hemoglobin adducts in African
American, Native Hawaiian, White, Japanese American, and Latino smokers from the Multiethic Cohort (MEC),
and to establish the role of the exposome in modifying lung cancer risk. Our approach is innovative because
we will, for the first time, characterize the totality of external and internal exposures using hemoglobin
adductomics in a large multiethnic group of smokers.
Expected outcomes: Our studies will help provide insight into the origins of ethnic variability in sensitivity to
smoking-mediated lung cancer and help identify specific risk factors that play the greatest role in modifying
lung cancer risk. An increased understanding of such risk factors may lead to preventative strategies that will
help overcome ethnic/racial disparities in lung cancer risk and improve human health.

## Key facts

- **NIH application ID:** 10411515
- **Project number:** 2P01CA138338-11
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** NATALIA Y TRETYAKOVA
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $348,260
- **Award type:** 2
- **Project period:** 2009-12-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10411515

## Citation

> US National Institutes of Health, RePORTER application 10411515, Untargeted Adductomics to Characterize Ethnic Differences in the Exposome of Smokers (2P01CA138338-11). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10411515. Licensed CC0.

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