Role of Acetaldehyde in the Development of Oral Cancer

Study Overview
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Brief Summary
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This is a minimal risk intervention study where healthy volunteers and individuals with Fanconi anemia will consume a single dose of alcohol and provide primarily non-invasive biological samples at various time points. Biospecimens to be collected include saliva, oral cells collected via mouthwash and cheek brush, and urine. The collection of two blood samples (5 mL each) will be optional and banked for future use.

Official Title
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Dissecting the Role of Acetaldehyde in Oral Carcinogenesis

Conditions
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Alcohol-Related Carcinoma, Fanconi Anemia, Oral Cavity Carcinoma

Intervention / Treatment
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* Drug: Alcohol
* Procedure: Biospecimen Collection
* Procedure: Breath Test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 21-45 years of age for alcohol drinkers Occasionally consume alcohol At least 1 drink per month for healthy volunteers At least 1 drink in the last 3 months for Fanconi anemia patients Meets one of the three criteria Healthy volunteer - ALDH2*1/1* homozygotes-not of Eastern Asian decent; Healthy volunteer - ALDH2*1/2* heterozygotes-of Eastern Asian decent and experience flushing when drinking Individual's with Fanconi anemia (FA). 18-45 years of age for non-drinkers Never consume alcohol/not had alcohol in the last 6 months Healthy volunteers. Non-smoker (smoked < 100 cigarettes in a lifetime) Exclusion Criteria: Pregnant or nursing Taking any medication or drug that might affect alcohol use and absorption or that might be affected by alcohol consumption Healthy volunteers who have taken any antibiotics in the last 3 months Currently consuming more than 21 drinks per week Have any history of alcohol or drug related problems Current or former tobacco/nicotine product(s) user Any regular use of tobacco/nicotine products or marijuana in the last year (cigarettes, e-cigarettes, cigars, pipes, smokeless tobacco) Trying or limited use of any nicotine products or marijuana in the last 1 month Active infection (influenza, cold, COVID, respiratory / sinus infection) - admission in the study will be delayed pending improved health Non-FA volunteers who have an unstable medical condition or condition that could be affected by alcohol consumption (insulin-dependent diabetes, ulcers, heart issues) Experience severe adverse events (nausea, blacking out) when consuming even low doses of alcohol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group I (alcohol consumption)<br>Participants who consume alcohol receive a standard drink or an alcohol dose that will result in a 0.03% BAC PO on study. Participants also undergo collection of saliva and breathalyzer testing throughout the trial. | Drug: Alcohol<br>* Alcohol dose given orally that will result in a 0.03% blood alcohol concentration (BAC).<br>Procedure: Biospecimen Collection<br>* Undergo saliva, mouthwash, and cheek brush collection<br>Procedure: Breath Test<br>* Undergo breathalyzer testing<br>|
| Active Comparator: Group II (biospecimen collection)<br>Participants who do not drink alcohol undergo collection of saliva, mouthwash, and cheek brush samples throughout the trial. | Procedure: Biospecimen Collection<br>* Undergo saliva, mouthwash, and cheek brush collection<br>Procedure: Breath Test<br>* Undergo breathalyzer testing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the acetaldehyde exposure to the oral cavity by comparing saliva levels before and after alcohol dose | Identify and quantify DNA adducts in the oral cells (mouthwash and cheek brush samples). | Prior to alcohol dose, and 30 minutes, 1 hour, 2 hours, 4 hours, and 6 hours post alcohol dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urine will be analyzed to confirm non-smoking status | The optional blood samples will be analyzed for DNA adducts in the blood. We will measure the total concentration of the marker NNAL in urine. | Prior to alcohol exposure | 
| Urine will be analyzed to confirm non-smoking status | The optional blood samples will be analyzed for DNA adducts in the blood. We will measure the total concentration of the marker NNAL in urine. | Up to 6 hours after alcohol exposure |