# Mechanisms of Ethnic/Racial Differences in Lung Cancer Due to Cigarette Smoking

> **NIH NIH P01** · UNIVERSITY OF MINNESOTA · 2020 · $1,951,087

## Abstract

ABSTRACT
This program project grant features a highly integrated team of scientists with diverse relevant expertise to
determine the mechanistic basis for the observed ethnic differences in susceptibility to lung cancer in cigarette
smokers. Their studies are based on a major lead form the Multiethnic Cohort study which demonstrated that,
for the same number of cigarettes smoked, and particularly at lower levels of smoking, self-identified African
Americans and Native Hawaiians have a higher incidence of lung cancer than Whites while Latinos and
Japanese Americans have a lower incidence. They will build on their important results from the first five years
of this project demonstrating significant differences in nicotine metabolism and carcinogen uptake which
partially explain the relatively high risk of African Americans and the low risk of Japanese Americans. Four
projects will draw on their expertise in epidemiology, genetics, epigenetics, biostatistics, analytical chemistry,
biochemistry, and tobacco carcinogenesis. Project 1, Ethnic Differences in Smoking-Related Biomarkers and
Risk of Lung Cancer, will evaluate whether DNA methylation profiles differ across racial/ethnic groups,
investigate the relationship between genome-wide DNA methylation and biomarkers of smoking dose, and the
relationship of nicotine metabolism, tobacco carcinogen and toxicant biomarkers, and DNA methylation to lung
cancer in current smokers. Project 2, 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) α-Hydroxy
Glucuronides, Metabolic Profiling and Activation, will determine the effect of CYP2A6 genotype on NNK
metabolic activation in Japanese American smokers with differing CYP2A6 activity, and use unique deuterated
NNK metabolic profiling methods to characterize NNK metabolism in these groups with diverse lung cancer
risk. Project 3, Ethnic/racial Differences in Metabolism and DNA Adduct Formation by 1,3-Butadiene, will
investigate ethnic differences in butadiene-DNA adducts in the urine of smokers from different ethnic groups
and determine the relationship of DNA adducts to lung cancer and the influence of carcinogen metabolizing
genes on DNA adduct formation, repair, and toxicity/mutagenicity. Project 4, Oral Cell DNA Adducts and
Urinary Biomarkers to Investigate Ethnic/Racial Differences in Lung Cancer Susceptibility, will quantify known
and previously unknown DNA adducts in oral mucosa cells of Native Hawaiian, White, and Japanese American
smokers and will investigate urinary biomarkers of acrolein, crotonaldehyde, inflammation, and oxidative
damage among smokers and non-smokers from these ethnic groups. These projects are supported by three
superb cores with unique world class expertise: Core A, Administrative; Core B, Clinical and Biomarkers; and
Core C, Biostatistics. In summary, we present a unique multidisciplinary approach to study mechanisms of
ethnic/racial differences in lung cancer susceptibility. We expect to continue to generate sound, exciting, a...

## Key facts

- **NIH application ID:** 9994187
- **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:** $1,951,087
- **Award type:** 5
- **Project period:** 2009-12-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994187

## Citation

> US National Institutes of Health, RePORTER application 9994187, Mechanisms of Ethnic/Racial Differences in Lung Cancer Due to Cigarette Smoking (5P01CA138338-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9994187. Licensed CC0.

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