Alcohol Exposure for Oral Cancer Risk

Overseen By Balbo Silvia, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Masonic Cancer Center, University of Minnesota

Must not be taking: Antibiotics, others

Disqualifiers: Pregnancy, Alcoholism, Tobacco use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

170 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that you do not take any medication or drug that might affect alcohol use and absorption or that might be affected by alcohol consumption. If you are on such medications, you may need to stop taking them to participate.

What data supports the effectiveness of the treatment Alcohol, Ethanol, Ethyl alcohol, Biospecimen Collection, Breath Test, Breath Test for Acetaldehyde, Acetaldehyde Breath Test for reducing oral cancer risk?

The research indicates that acetaldehyde, a byproduct of alcohol, is linked to an increased risk of oral cancer, as it can cause harmful changes in DNA. However, there is no evidence suggesting that alcohol or its components reduce oral cancer risk; instead, they may increase it. ^{1 2 3 4 5}

Is alcohol exposure safe for humans in clinical trials?

Alcohol consumption leads to the production of acetaldehyde, a substance that is considered carcinogenic (cancer-causing) to humans. Studies show that even small amounts of alcohol can increase acetaldehyde levels in the mouth, which is linked to a higher risk of oral cancer. Therefore, alcohol exposure is not considered safe due to its potential to cause cancer. ^{1 2 4 6 7}

How does alcohol exposure differ from other treatments for oral cancer risk?

Alcohol exposure is unique because it involves the consumption of alcohol, which leads to the production of acetaldehyde, a substance that can damage DNA and increase cancer risk. Unlike traditional treatments that aim to reduce cancer risk, alcohol exposure itself is a risk factor for oral cancer due to its carcinogenic effects. ^{1 2 4 7 8}

Eligibility Criteria

This trial is for healthy volunteers and individuals with Fanconi anemia who occasionally drink alcohol. Participants should be non-smokers, aged 18-45 (21-45 for drinkers), and not have used antibiotics or experienced severe reactions to alcohol recently. Pregnant or nursing individuals, heavy drinkers, those with unstable health conditions affected by alcohol, or recent tobacco/nicotine users are excluded.

Inclusion Criteria

You drink alcohol at least once a month.

You have consumed at least one alcoholic drink in the past three months and have Fanconi anemia.

I am either a healthy volunteer with specific genetic traits, of Eastern Asian descent with alcohol flushing, or have Fanconi anemia.

Exclusion Criteria

You are currently drinking more than 21 drinks per week.

I currently do not have any active infections like the flu, cold, or COVID.

I am healthy but have taken antibiotics in the past 3 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Intervention

Participants consume a single dose of alcohol and provide non-invasive biological samples at various time points

1 day

1 visit (in-person)

Sample Collection

Collection of saliva, oral cells via mouthwash and cheek brush, and urine at specified time points

6 hours

Multiple time-point collections during the visit

Follow-up

Participants are monitored for safety and effectiveness after intervention

1 week

Treatment Details

Interventions

• Alcohol
• Biospecimen Collection
• Breath Test

Trial Overview The study investigates how acetaldehyde contributes to oral cancer development after consuming a single dose of alcohol. It involves collecting saliva, mouthwash cells, cheek brush cells, urine samples from participants at different times post-consumption. Blood sample collection is optional.

Participant Groups

Group I: Group I (alcohol consumption) Experimental Treatment 3 Interventions

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.

Group II: Group II (biospecimen collection) Active Control 2 Interventions

Participants who do not drink alcohol undergo collection of saliva, mouthwash, and cheek brush samples throughout the trial.

Who Is Running the Clinical Trial?

Masonic Cancer Center, University of Minnesota

Lead Sponsor

Trials

285

Recruited

15,700+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Findings from Research

In a study involving 10 healthy nonsmokers, levels of the DNA adduct N(2)-ethylidene-dGuo increased significantly (up to 100-fold) within 4 hours after alcohol consumption, indicating a strong dose-responsive relationship with acetaldehyde exposure.

These findings provide important evidence of how alcohol consumption leads to DNA damage in oral cells, supporting the link between acetaldehyde and the risk of head and neck cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kinetics of DNA adduct formation in the oral cavity after drinking alcohol. Balbo, S., Meng, L., Bliss, RL., et al.[2021]

This study found that using alcohol-containing mouthwashes significantly increases acetaldehyde levels in saliva, reaching concentrations similar to those found after consuming alcoholic beverages, with peak levels observed at 2 minutes post-use.

While the overall systemic exposure to acetaldehyde from mouthwash use is low and poses a minimal public health risk, the local concentrations in the mouth could potentially lead to DNA damage and increase the risk of oral cancer, raising concerns about their long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salivary acetaldehyde increase due to alcohol-containing mouthwash use: a risk factor for oral cancer. Lachenmeier, DW., Gumbel-Mako, S., Sohnius, EM., et al.[2016]

Individuals with aldehyde dehydrogenase 2 deficiency, known as 'flushers', exhibit significantly higher levels of acetaldehyde in their breath after rinsing their mouths with alcohol compared to nonflushers, indicating a potential risk for increased mutagenic DNA lesions.

The study found that even without alcohol ingestion, local exposure to alcohol in the mouth leads to elevated acetaldehyde levels in flushers, which may contribute to a higher risk of head and neck cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Alcohol Sensitivity in Healthy Young Adults on Breath Pharmacokinetics of Acetaldehyde After Mouth Washing with Alcohol. Himemiya-Hakucho, A., Tanaka, T., Liu, J., et al.[2019]

Smokers have significantly higher levels of salivary acetaldehyde after consuming alcohol compared to nonsmokers, indicating that smoking increases the carcinogenic potential of alcohol consumption.

When smokers also smoke while drinking alcohol, their salivary acetaldehyde levels rise dramatically, suggesting a synergistic effect that may contribute to a higher risk of upper digestive tract cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic effect of alcohol drinking and smoking on in vivo acetaldehyde concentration in saliva. Salaspuro, V., Salaspuro, M.[2016]

Moderate ethanol ingestion leads to significant production of acetaldehyde in saliva, which may contribute to the increased risk of upper gastrointestinal tract cancer, as acetaldehyde is known to be mutagenic and carcinogenic.

The study found that using an antiseptic mouthwash (chlorhexidine) for three days significantly reduced acetaldehyde production, suggesting that oral hygiene may play a role in mitigating the cancer risk associated with alcohol consumption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High acetaldehyde levels in saliva after ethanol consumption: methodological aspects and pathogenetic implications. Homann, N., Jousimies-Somer, H., Jokelainen, K., et al.[2022]

Sipping strong alcoholic beverages, especially those high in acetaldehyde like calvados, leads to significantly higher salivary acetaldehyde concentrations compared to beverages without acetaldehyde, indicating immediate carcinogenic exposure.

This study found that carcinogenic levels of acetaldehyde can persist in saliva for at least 10 minutes after consumption, highlighting the potential risks associated with even small amounts of strong alcoholic drinks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A single sip of a strong alcoholic beverage causes exposure to carcinogenic concentrations of acetaldehyde in the oral cavity. Linderborg, K., Salaspuro, M., Väkeväinen, S.[2013]

Acetaldehyde, a byproduct of alcohol consumption and a known group 1 carcinogen, significantly increases the risk of upper gastrointestinal cancers, especially in individuals with certain genetic mutations affecting alcohol metabolism.

Preventive measures can effectively reduce acetaldehyde exposure, highlighting the importance of regulatory actions and consumer education in cancer prevention strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interactions of alcohol and tobacco in gastrointestinal cancer. Salaspuro, M.[2017]

Short-term exposure to ethanol concentrations between 10% and 15% can cause significant cytotoxic effects on human epithelial cells, which may explain the local carcinogenic effects of alcohol in tissues like the oral cavity and esophagus.

To reduce the risk of cancers associated with alcohol consumption, it may be beneficial to choose alcoholic beverages with lower ethanol concentrations or dilute drinks to non-cytotoxic levels, potentially also mitigating the combined risks of alcohol and tobacco use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avoiding the ingestion of cytotoxic concentrations of ethanol may reduce the risk of cancer associated with alcohol consumption. Guillén-Mancina, E., Calderón-Montaño, JM., López-Lázaro, M.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Kinetics of DNA adduct formation in the oral cavity after drinking alcohol. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Salivary acetaldehyde increase due to alcohol-containing mouthwash use: a risk factor for oral cancer. [2016]

3. England pubmed.ncbi.nlm.nih.gov

Effect of Alcohol Sensitivity in Healthy Young Adults on Breath Pharmacokinetics of Acetaldehyde After Mouth Washing with Alcohol. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Synergistic effect of alcohol drinking and smoking on in vivo acetaldehyde concentration in saliva. [2016]

5. England pubmed.ncbi.nlm.nih.gov

High acetaldehyde levels in saliva after ethanol consumption: methodological aspects and pathogenetic implications. [2022]

6. England pubmed.ncbi.nlm.nih.gov

A single sip of a strong alcoholic beverage causes exposure to carcinogenic concentrations of acetaldehyde in the oral cavity. [2013]

7. Australia pubmed.ncbi.nlm.nih.gov

Interactions of alcohol and tobacco in gastrointestinal cancer. [2017]

8. Ireland pubmed.ncbi.nlm.nih.gov

Avoiding the ingestion of cytotoxic concentrations of ethanol may reduce the risk of cancer associated with alcohol consumption. [2018]