Oral Cell DNA Adducts in Smokers

Lung Cancer Clinical Trial

— OCDNA  

Official title:

Quantitation of Oral Cell DNA Adducts in Smokers

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03285893
• Other study ID #: 2017NTLS019
• Status: Not yet recruiting
• Start date: June 1, 2023
• Est. completion date: January 31, 2027

Study information

• Verified date: September 2022
• Source: University of Minnesota
• Contact: Joni Jensen, MPH
• Phone: 612-624-5178
• Email: jense010[@]umn.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

1. 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.

2. 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 300
• Est. completion date: January 31, 2027
• Est. primary completion date: October 31, 2026
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lung Cancer

Intervention

Other:
• oral cell DNA adducts
oral cells will be collected, DNA isolated, and analyzed for adducts

Locations

Country	Name	City	State
United States	Tobacco Use Research Center	Minneapolis	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
University of Minnesota	University of Hawaii

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Quantitation of oral cell DNA adducts	DNA adducts of acrolein, formaldehyde, and tobacco-specific compounds	Baseline
Secondary	Urinary metabolites	Metabolites of acrolein crotonaldehyde, oxidative damage and inflammation	Baseline