Risk Assessment Methods for Stomach Cancer
Recruiting in Palo Alto (17 mi)
Overseen byYanghee Woo
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: City of Hope Medical Center
Disqualifiers: Non-Hispanic White, Gastric cancer, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This clinical trial evaluates the usefulness of various risk assessment tests, including Helicobacter pylori (H. pylori) breath testing, questionnaires, and endoscopies for identifying participants at high risk for stomach cancer. H. pylori is a bacteria that causes stomach inflammation and ulcers in the stomach. People with H. pylori infections may be more likely to develop cancer in the stomach. H. pylori breath testing can help identify the presence of H. pylori infection in a participant and help identify if the participant may be at a higher risk of developing stomach cancer. An endoscopy uses a thin, flexible lighted tube that is inserted inside the esophagus, stomach, and first part of the small intestine. This allows the doctor to see and look for abnormal areas that may need to be biopsied. Risk assessment including H. pylori evaluation, questionnaires, and endoscopies may help identify participants at high risk for stomach cancer and may be a useful screening tool for earlier stomach cancer diagnosis.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
Is the acetaldehyde breath test safe for humans?
The acetaldehyde breath test involves exposure to acetaldehyde, which is considered a carcinogen (a substance that can cause cancer) in humans. Acetaldehyde is linked to an increased risk of cancers in the digestive tract, especially in individuals with certain genetic traits or conditions. Therefore, the safety of this test should be carefully evaluated, especially for those at higher risk.
12345Is the treatment in the trial 'Risk Assessment Methods for Stomach Cancer' a promising treatment?
The research articles focus on acetaldehyde, a chemical linked to cancer risk, especially in people with certain genetic traits. They suggest that understanding and measuring acetaldehyde levels could help in assessing cancer risk, which might be useful in developing new treatments or prevention strategies for stomach cancer. However, the articles do not directly mention a specific treatment being tested in the trial, so it's unclear if a particular treatment is promising based on this information.
12678Eligibility Criteria
This trial is for individuals who may be at high risk of developing stomach cancer. It's particularly focused on those who might have an infection with H. pylori, a bacteria linked to stomach ulcers and cancer.Inclusion Criteria
Documented informed consent of the participant and/or legally authorized representative
Assent, when appropriate, will be obtained per institutional guidelines
Identify as a racial minority either Asian, Hispanic, or Black American
+2 more
Exclusion Criteria
History of upper endoscopy within 2 years
A direct study team member
An employee who is under the direct/indirect supervision of the principal investigator (PI)/a coinvestigator/the study manager
+4 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
At time of screening up to 3 years
Initial Risk Assessment
Participants complete questionnaires, undergo collection of a blood sample, and undergo an H. pylori breath test for gastric cancer risk assessment at baseline
Baseline
1 visit (in-person)
Cohort I - EGD and Biopsy
High-risk participants may undergo esophagogastroduodenoscopy (EGD) with possible tissue biopsy within 3 months of baseline risk assessment and complete questionnaires annually up to 3 years
3 months for EGD, annually up to 3 years for questionnaires
Cohort II - Questionnaires
Non-high risk participants complete questionnaires for re-assessment annually up to 3 years and may undergo EGD at year 2
Annually up to 3 years
Follow-up
Participants are monitored annually for a total of 3 years
3 years
Participant Groups
The study tests the effectiveness of various methods like breath tests for H. pylori, questionnaires about health history, and endoscopies (a tube with a camera inserted through the mouth) to find people at high risk for stomach cancer.
3Treatment groups
Experimental Treatment
Active Control
Group I: Part II, Cohort I (EGD, biopsy)Experimental Treatment3 Interventions
Participants may undergo EGD with possible tissue biopsy within 3 months of baseline risk assessment and complete questionnaires annually up to 3 years.
Group II: Part I (initial risk assessment)Experimental Treatment3 Interventions
Participants complete questionnaires, undergo collection of a blood sample, and undergo an H. pylori breath test for gastric cancer risk assessment at baseline.
Group III: Part II, Cohort II (questionnaires)Active Control2 Interventions
Participants complete questionnaires for re-assessment annually up to 3 years and may undergo EGD at year 2.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
City of Hope Medical CenterDuarte, CA
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Who Is Running the Clinical Trial?
City of Hope Medical CenterLead Sponsor
National Cancer Institute (NCI)Collaborator
References
The determination of acetaldehyde in exhaled breath. [2019]Breath acetaldehyde has been used to investigate the production of acetaldehyde after ethanol ingestion in ALDH2-deficient individuals, to compare ethanol and acetaldehyde metabolism, to study the toxicological outcome of metabolic inhibitors of ALDH2, and as a biomarker of exposure to ethanol vapours. A number of approaches have been developed to collect representative breath samples (mixed air or alveolar air) and to measure breath acetaldehyde. For instance, the highest breath concentration of acetaldehyde (approximately 50 nmoles/1) measured during pulmonary ethanol exposure (1000ppm, 6 hours) is of the same magnitude as those measured after ingestion of 0.4-0.8 g/kg (-60-80 nmoles/ i), whereas endogenous levels rarely exceed 1 nmole/l. The interpretation of breath acetaldehyde is compounded by several factors; smoking, ALDH2 polymorphism and alcohol drinking habits are associated with higher breath/blood levels. Some authors have considered that breath acetaldehyde, particularly low levels, cannot be used to estimate blood acetaldehyde. Despite the problems associated with its determination, breath acetaldehyde could be an interesting tool for estimating ethanol or acetaldehyde exposure. However, some additional research efforts will be necessary in order to standardize the technique used for breath sampling and to control the influence of the factors that are known to affect breath acetaldehyde determination.
ALDH2-deficiency as genetic epidemiologic and biochemical model for the carcinogenicity of acetaldehyde. [2018]Humans are cumulatively exposed to acetaldehyde from various sources including alcoholic beverages, tobacco smoke, foods and beverages. The genetic-epidemiologic and biochemical evidence in ALDH2-deficient humans provides strong evidence for the causal relationship between acetaldehyde-exposure due to alcohol consumption and cancer of the upper digestive tract. The risk assessment has so far relied on thresholds based on animal toxicology with lower one-sided confidence limit of the benchmark dose values (BMDL) typically ranging between 11 and 63 mg/kg bodyweight (bw)/day dependent on species and endpoint. The animal data is problematic for regulatory toxicology for various reasons (lack in study quality, problems in animal models and appropriateness of endpoints - especially cancer - for transfer to humans). In this study, data from genetic epidemiologic and biochemical studies are reviewed. The increase in the daily exposure dose to acetaldehyde in alcohol-consuming ALDH2-deficients vs. ALDH2-actives was about twofold. The acetaldehyde increase due to ALDH2 inactivity was calculated to be 6.7 μg/kg bw/day for heavy drinkers, which is associated with odds ratios of up to 7 for head and neck as well as oesophageal cancer. Previous animal toxicology based risk assessments may have underestimated the risk of acetaldehyde. Risk assessments of acetaldehyde need to be revised using this updated evidence.
Acetaldehyde and gastric cancer. [2013]Aldehyde dehydrogenase (ALDH2) and alcohol dehydrogenase (ADH) gene polymorphisms associating with enhanced acetaldehyde exposure and markedly increased cancer risk in alcohol drinkers provide undisputable evidence for acetaldehyde being a local carcinogen not only in esophageal but also in gastric cancer. Accordingly, acetaldehyde associated with alcoholic beverages has recently been classified as a Group 1 carcinogen to humans. Microbes are responsible for the bulk of acetaldehyde production from ethanol both in saliva and Helicobacter pylori-infected and achlorhydric stomach. Acetaldehyde is the most abundant carcinogen in tobacco smoke and it readily dissolves into saliva during smoking. Many foodstuffs and 'non-alcoholic' beverages are important but unrecognized sources of local acetaldehyde exposure. The cumulative cancer risk associated with increasing acetaldehyde exposure suggests the need for worldwide screening of the acetaldehyde levels of alcoholic beverages and as well of the ethanol and acetaldehyde of food produced by fermentation. The generally regarded as safe status of acetaldehyde should be re-evaluated. The as low as reasonably achievable principle should be applied to the acetaldehyde of alcoholic and non-alcoholic beverages and food. Risk groups with ADH-and ALDH2 gene polymorphisms, H. pylori infection or achlorhydric atrophic gastritis, or both, should be screened and educated in this health issue. L-cysteine formulations binding carcinogenic acetaldehyde locally in the stomach provide new means for intervention studies.
Acetaldehyde as a common denominator and cumulative carcinogen in digestive tract cancers. [2021]The key issue in cancer prevention is the identification of specific aetiologic factors. Acetaldehyde, the first metabolite of ethanol oxidation, is carcinogenic in animals. ADH and ALDH2 gene mutations provide an exceptional human model to estimate the long-term effects of acetaldehyde exposure in man. These models provide strong evidence for the local carcinogenic potential of acetaldehyde also in humans. Ethanol is metabolized to acetaldehyde by both mucosal and microbial enzymes. Many microbes produce acetaldehyde from ethanol, but their capacity to eliminate acetaldehyde is low, which leads to the accumulation of acetaldehyde in saliva during an alcohol challenge. Acetaldehyde is the most abundant carcinogen in tobacco smoke, and it readily dissolves into saliva during smoking. Fermented food and many alcoholic beverages can also contain significant amounts of acetaldehyde. Thus acetaldehyde, derived from mucosal or microbial oxidation of ethanol, tobacco smoke, and/or diet, appears to act as a cumulative carcinogen in the upper digestive tract of humans. The evidence strongly suggests the importance of world-wide screening of acetaldehyde and ethanol levels in many beverages and foodstuffs, as well as an urgent need for regulatory measures and consumer guidance. Screening of the risk groups with enhanced acetaldehyde exposure, e.g. people with ADH and ALDH2 gene polymorphisms and hypochlorhydric atrophic gastritis, should also be seriously considered. Most importantly, the GRAS (generally regarded as safe) status of acetaldehyde, which allows it to be used as a food additive, should be re-evaluated, and the classification of acetaldehyde as a carcinogen should be upgraded.
Effects of acetaldehyde inhalation in mitochondrial aldehyde dehydrogenase deficient mice (Aldh2-/-). [2022]Human body might be exposed to acetaldehyde from smoking or occupational environment, which is known to be associated with cancer through the formation of DNA adducts, in particular, N2-ethylidene-2'- deoxyguanosine (N2-ethylidene-dG). Aldehyde dehydrogenase 2 (ALDH2) is the major enzyme that contribute to the detoxification of acetaldehyde in human body. In this study, wild type (Aldh2+/+) and Aldh2KO (Aldh2-/-) mice were exposed to the air containing 0, 125, 500 ppm acetaldehyde for 2 weeks. After inhalation, levels of N2- ethylidene-dG in the chromosomal DNA were analyzed by liquid chromatography tandem mass spectrometry (LC/MS/MS). N2-ethylidene-dG levels in livers of Aldh2-/- mice were always lower than those of Aldh2+/+ mice, suggesting that Aldh2 deficiency might cause the induction of acetaldehyde metabolizing enzymes in the liver such as P450s. The differences between Aldh2-/- and Aldh2+/+ mice were greater in the order of nasal epithelium > lung > dorsal skin, suggesting that nasal epithelium and lung are the major target sites for acetaldehyde. Acetaldehyde inhalation may cause a high risk in nasal epithelium and lung cancers for individuals with inactive ALDH2.
A longitudinal study of ethanol and acetaldehyde in the exhaled breath of healthy volunteers using selected-ion flow-tube mass spectrometry. [2013]Selected-ion flow-tube mass spectrometry (SIFT-MS) has been used to monitor the volatile compounds in the exhaled breath of 30 volunteers (19 male, 11 female) over a 6-month period. Volunteers provided breath samples each week between 8:45 and 13:00 (before lunch), and the concentrations of several trace compounds were obtained. In this paper the focus is on ethanol and acetaldehyde, which were simultaneously quantified by SIFT-MS using H3O+ precursor ions. The mean ethanol level for all samples was 196 parts-per-billion (ppb) with a standard deviation of 244 ppb, and the range of values for breath samples analysed is 0 to 1663 ppb. The mean acetaldehyde level for all samples was 24 ppb with a standard deviation of 17 ppb, and the range of values for breath samples analysed is 0 to 104 ppb. Background (ambient air) levels of ethanol were around 50 ppb, whereas any background acetaldehyde was usually undetectable. Increased ethanol levels were observed if sweet drink/food had been consumed within the 2 h prior to providing the breath samples, but no increase was apparent when alcohol had been consumed the previous evening. The measured endogenous breath ethanol and acetaldehyde levels were not correlated. These data relating to healthy individuals are a prelude to using breath analysis for clinical diagnosis, for example, the recognition of bacterial overload in the gut (ethanol) or the possibly of detecting tumours in the body (acetaldehyde).
Breath and blood acetaldehyde concentrations and their correlation during normal and calcium carbimide-modified ethanol oxidation in man. [2019]With the use of new and improved analytical techniques, concentrations of acetaldehyde in antecubital venous blood and breath of human volunteers were measured after (a) pretreatment of subjects with ethanol and the aldehyde dehydrogenase inhibitor, calcium carbimide and (b) treatment with ethanol only. Breath acetaldehyde concentrations were converted to equivalent pulmonary blood concentrations using an experimentally determined blood: breath partition ratio for acetaldehyde of 190. Under all experimental conditions, blood acetaldehyde concentrations calculated from breath analysis were seen to closely reflect those measured by direct blood analysis. Treatment of subjects with calcium carbimide resulted in elevated blood and breath acetaldehyde concentrations which were rapidly lowered by the intravenous infusion of 4-methyl pyrazole. Peak blood acetaldehyde concentrations ranged from 25 to 188 muM after calcium carbimide and ethanol treatment, but were only 6-11 muM after ethanol treatment alone (1.2g/kg).
Measuring and reporting the concentration of acetaldehyde in human breath. [2013]Most of the acetaldehyde generated during the metabolism of ethanol becomes tightly bound to endogenous molecules such as haemoglobin, amino acids and certain phospholipids. Free acetaldehyde passes the blood-brain barrier and traces of this toxic metabolite are excreted through the lungs and can be detected in the expired air. The blood/air partition coefficient of acetaldehyde at 34 degrees C, the average temperature of end-expired air, is about 190:1. Because of various problems associated with measuring acetaldehyde in blood samples, several research groups have instead investigated the analysis of acetaldehyde in breath which offers an indirect and alternative approach for clinical and research purposes. However, care is needed when interpreting the results of breath acetaldehyde measurements, because of the possibility of local formation from microflora inhabiting the upper airways and mouth. The concentration of acetaldehyde exhaled in breath after drinking alcohol demonstrates large inter-individual differences depending on various genetic (racial) and environmental factors. Moreover, acetaldehyde is an endogenous metabolite and even without drinking any alcohol the concentrations expelled in breath span from 0.2 to 0.6 nmol/l, with higher levels observed in smokers and abstinent alcoholics. Breath acetaldehyde concentration reached between 5 and 50 nmol/l in European subjects who drank a moderate dose of ethanol (0.4-0.8 g/kg), with the highest values seen in smokers. The concentration of breath acetaldehyde in Japanese subjects after drinking alcohol reached between 200 and 500 nmol/l at the peak. These much higher levels follow because a large proportion of Orientals (40-50%) inherit an inactive form of the low Km mitochondrial isoenzyme of aldehyde dehydrogenase (ALDH2). The highest concentration of breath acetaldehyde were seen in healthy Caucasians who drank a small dose of alcohol (0.25 g/kg) after taking the alcohol-sensitizing drug calcium carbimide, which blocks the action of ALDH isozymes. During the most intense acetaldehyde-flush reaction, breath acetaldehyde reached between 200 and 1300 nmol/l, but even these abnormally high concentrations did not interfere with the analysis of ethanol in breath by means of non-specific infrared analysers currently used in many countries for testing drinking drivers.