Oral Cell DNA Adducts in Smokers

Study Overview
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Brief Summary
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DNA adducts in the oral mucosa cells of 100 smokers from 3 ethnic groups - Native Hawaiians, Whites, and Japanese Americans with differing risks for lung cancer upon cigarette smoking will be quantified. DNA adducts of tobacco smoke carcinogens will be quantified using both targeted and untargeted approaches.

Detailed Description
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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 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. Using a targeted DNA adductomic method, 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, apply DNA adductomic methods in an untargeted mode to investigate the presence of previously unknown DNA adducts. The unknown adducts detected by the untargeted analysis will be included in the list of targeted DNA adducts to ultimately obtain a sensitive method to assess overall DNA damage resulting from cigarette smoking. The list of DNA adducts created in Specific Aim 3a will be applied to investigate differences in the DNA damage signature in selected samples analyzed in Specific Aim 1.

Official Title
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Quantitation of Oral Cell DNA Adducts in Smokers

Conditions
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Lung Cancer

Intervention / Treatment
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* Other: oral cell DNA adducts


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: currently smoke at least 5 cigarettes per day, self-identified Japanese Americans, European Americans, or Native Hawaiians. Exclusion Criteria: no current use of other nicotine containing products, no acute or uncontrolled medical or psychiatric conditions, no greater than 14 alcoholic drinks per week, not pregnant, not breastfeeding, not currently taking any medications that affect relevant metabolic enzymes, no active infection.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Native Hawaiian cigarette smokers<br>oral cell DNA adducts | Other: oral cell DNA adducts<br>* oral cells will be collected, DNA isolated, and analyzed for adducts<br>|
| White (European Americans) cigarette smokers<br>oral cell DNA adducts | Other: oral cell DNA adducts<br>* oral cells will be collected, DNA isolated, and analyzed for adducts<br>|
| Japanese American cigarette smokers<br>oral cell DNA adducts | Other: oral cell DNA adducts<br>* oral cells will be collected, DNA isolated, and analyzed for adducts<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantitation of oral cell DNA adducts | DNA adducts of acrolein, formaldehyde, and tobacco-specific compounds | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary metabolites | Metabolites of acrolein crotonaldehyde, oxidative damage and inflammation | Baseline |