Oral Cell DNA Adducts in Smokers (OCDNA)

Quantitation of Oral Cell DNA Adducts in Smokers

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Lung Cancer
• Intervention / Treatment: Other: oral cell DNA adducts

Detailed 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.

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

• Study Contact: Name: Joni Jensen, MPH; Phone Number: 612-624-5178; Email: jense010@umn.edu
• Study Contact Backup: Name: Stephen S Hecht, Ph.D; Phone Number: 612-624-7604; Email: hecht002@umn.edu

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Tobacco Use Research Center
      • Contact: Joni A Jensen, MPH; Phone Number: 612-624-5178; Email: jense010@umn.edu
      • Contact: Stephen S Hecht, Ph.D.; Phone Number: 612-624-7604; Email: hecht002@umn.edu
      • Principal Investigator: Stephen S Hecht, Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

100 each of three ethnic groups: Native Hawaiians, Japanese Americans, whites

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Native Hawaiian cigarette smokers; oral cell DNA adducts	Other: oral cell DNA adducts; oral cells will be collected, DNA isolated, and analyzed for adducts
White (European Americans) cigarette smokers; oral cell DNA adducts	Other: oral cell DNA adducts; oral cells will be collected, DNA isolated, and analyzed for adducts
Japanese American cigarette smokers; oral cell DNA adducts	Other: oral cell DNA adducts; oral cells will be collected, DNA isolated, and analyzed for adducts

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Minnesota
• Collaborators: University of Hawaii
• Investigators: Principal Investigator: Stepehn Hecht, PhD, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2023
• Primary Completion (Anticipated): October 31, 2026
• Study Completion (Anticipated): January 31, 2027

Study Registration Dates

• First Submitted: September 1, 2017
• First Submitted That Met QC Criteria: September 14, 2017
• First Posted (Actual): September 18, 2017

Study Record Updates

• Last Update Posted (Actual): September 30, 2022
• Last Update Submitted That Met QC Criteria: September 29, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: 2017NTLS019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Only unidentified data will be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No