Metabolism of NNK Among African Americans

NCT01158456 | Completed DMC

• 2 other identifiers: 2010NTLS0561P01CA138338-01A1
• Study Type: observational
• Target: 161
• Locations: 1 country
• Sites: 1

Brief Summary

Metabolism and DNA adduct formation are critical in cancer induction by NNK. The investigators goal is to understand whether the observed ethnic/racial differences in lung cancer incidence are due to variations in NNK metabolism. The investigators overall hypothesis is that cancer susceptibility relates to carcinogen dose and to the balance between carcinogen metabolic activation and detoxification. The investigators propose to test this hypothesis via investigation of potential differences in NNK metabolic activation and detoxification in African American and European American smokers.

Conditions

Lung Cancer

Keywords

smoking; lung cancer; ethnic racial differences; tobacco specific nitrosamines; metabolism of carcinogens

Outcome Measures

Primary Outcomes (1)

• Conduct a comprehensive analysis of urinary biomarkers of NNK metabolic activation and detoxification in African American and European American smokers.

  We will recruit smokers to smoke specially prepared cigarettes containing \[pyridine-D4\]NNK, and measure deuterium-labeled NNK metabolites in the urine of these subjects. The rationale for the use of deuterium-labeled NNK is that we need to specifically identify NNK-derived metabolites, because these biomarkers are also formed as a result of nicotine metabolism. Our overall hypothesis is that the relative contribution of the biomarkers of NNK metabolic activation to the total amount of NNK metabolites will be higher in African Americans as compared to European Americans.

  10 days

Secondary Outcomes (2)

• Measure in exfoliated oral mucosa cells of African American and European American smokers DNA adducts formed as a result of NNK metabolic activation.

  10 days

• Assess the repair of NNK-induced DNA damage.

  10 days

Study Arms (2)

African Americans

Subjects will be classified as African American if they report themselves, biological parents and both sets of biological grandparents as African American or African descent.

European American

Subjects will be classified as European American if they report themselves, biological parents and both sets of biological grandparents as European American or European descent.

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Subjects will be classified as African American if they report themselves, biological parents and both sets of biological grandparents as African American or African descent. Similar criteria will be applied to European Americans (e.g., self, both parents and four grandparents of European American or European descent). Subjects will be evenly divided by gender.

You may qualify if:

• Male or female subjects with a smoking history of at least 10 cigarettes daily for at least 1 year;
• Subjects report themselves, biological parents and both sets of biological grandparents as
• African American or African descent or
• European American or European descent
• Subjects are in apparently good physical health (no unstable medical condition)
• Subjects are in stable, good mental health (e.g. not currently, within the past 6 months, experiencing unstable or untreated psychiatric diagnosis, including substance abuse, as determined by the PRIME-MD);
• Subjects have provided written informed consent to participate in the study.

You may not qualify if:

• Unstable medical conditions including cancer, coronary heart disease and arrhythmia
• Cannot or unwilling to identify ethnic/racial ancestry
• Women who are currently pregnant or breast feeding
• Currently using any other tobacco or nicotine-containing product
• Currently taking any medications that affect relevant metabolic enzymes.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Tobacco Research Programs University of Minnesota

Minneapolis, Minnesota, 55414, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Venous blood sample (approximately 40 ml) will be drawn from each study participant at the baseline visit. Approximately 33 ml will be used immediately for the study, and the remaining two 3-ml volumes will be reserved for future use. The various components of the blood including buffy coat (white blood cells), red blood cells, plasma, and serum will be separated immediately after their collection, labelled using a unique subject number, and stored in a -80C freezer. Urine samples and oral cells will be collected from study subjects at various time points. All these samples will be labelled using a unique subject number, and stored at a -80C freezer.

MeSH Terms

Conditions

Lung Neoplasms; Smoking

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Behavior

Study Officials

• Dorothy K Hatsukami, Ph.D.

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2010
• First Posted: July 8, 2010
• Study Start: December 1, 2010
• Primary Completion: September 1, 2014
• Study Completion: November 1, 2017
• Last Updated: April 10, 2023

Record last verified: 2023-04

Locations

US (1)