# Project 1 - Ethnic Differences in Smoking-Related Biomarkers and Risk of Lung Cancer

> **NIH NIH P01** · UNIVERSITY OF MINNESOTA · 2020 · $839,292

## Abstract

ABSTRACT 
Worldwide, lung cancer is the most common cancer and the leading cause of cancer-related deaths. While, 
cigarette smoking is the primary risk factor for this disease, only 15-20% of smokers will develop lung cancer. 
Moreover, we showed in the Multiethnic Cohort (MEC) Study that, on the average and for the same quantity of 
cigarette smoke, compared to whites, African Americans and Native Hawaiians have a 50% greater risk of 
developing lung cancer; whereas, Japanese Americans and Latinos have a 25% lower risk of the disease. In 
the prior funding period, we found that internal smoking dose, as measured by urinary total nicotine equivalents 
(TNE), was highest in African Americans and lower in Japanese Americans. This correlates with their 
population lung cancer risks. However, in Native Hawaiians and Latinos among biomarkers of internal smoking 
dose and tobacco toxicant exposure and metabolism, only the biomarkers for acrolein and crotoaldehyde 
correlated with directionality of lung cancer risk. Our preliminary DNA methylation data suggests that smoking 
dose may influence the epigenome differentially across racial/ethnic groups. Additionally, our preliminary 
analysis in MEC suggested that biomarkers of internal smoking dose over time (TNE-years) and of nicotine 
metabolism (cytochrome P450 2A6 activity) are associated with an increased risk of lung cancer, even after 
adjusting for self-reported measures of smoking dose (pack-years). The objectives of the proposed study are 
to identify biomarkers that are associated with smoking-related lung cancer risk and to improve our 
understanding of the mechanisms underlying the ethnic/racial differences in lung cancer risk. We propose to 
conduct an epigenome-wide association study of blood leukocyte DNA methylation with smoking dose and 
biomarkers of tobacco toxicant exposure and metabolism (Aim 1). We will also systematically investigate the 
association of biomarkers of tobacco toxicant exposure and metabolism (n=1,865 cases and 3,619 controls) 
and DNA methylation in blood leukocytes (n=1,600 cases and 3,354 controls) with lung cancer risk (Aim 2). 
Additionally, any biomarkers identified in the other projects (e.g. Projects 3 and 4: urinary DNA adducts of 1,3- 
butadiene, acrolein, and crotoaldehyde) that show a promise towards explaining the difference in disease risk 
will also be evaluated for potential associations with risk of lung cancer. We hypothesize that ethnic/racial and 
individual differences in lung cancer risk are due to disparate biological response to common tobacco lung 
toxicants, which will be reflected by variations in biomarkers of smoking dose, tobacco toxicant exposure and 
metabolism, and DNA methylation profiles. The findings from this study will expand our understanding of the 
smoking-related mechanisms of lung cancer and the ethnic/racial differences in lung cancer risk. The 
identification of risk biomarkers will aid in the development of novel smoking...

## Key facts

- **NIH application ID:** 9994211
- **Project number:** 5P01CA138338-10
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Sungshim Lani Park
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $839,292
- **Award type:** 5
- **Project period:** — → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994211

## Citation

> US National Institutes of Health, RePORTER application 9994211, Project 1 - Ethnic Differences in Smoking-Related Biomarkers and Risk of Lung Cancer (5P01CA138338-10). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9994211. Licensed CC0.

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