Acetaldehyde/ethanol breath test for identifying people at high risk of upper aerodigestive tract cancer.

18 Background: Alcohol drinking increases the risk of upper aerodigestive tract cancer, and acetaldehyde (a metabolite of alcohol) is a definite carcinogen for this type of cancer. Acetaldehyde is formed mainly by the oxidation of ethanol by alcohol dehydrogenase 1B (ADH1B) and is eliminated by aldehyde dehydrogenase 2 (ALDH2) in the liver. About 50% of Asian people have the ALDH2*2 variant allele, which encodes an inactive enzyme. Those with the ALDH2*2 allele and an alcohol drinking habit are at definite risk of esophageal and head and neck cancers. Genetic testing is the most reliable method for identifying the ALDH2 genotype, but it is not practical for mass screening because of the cost and time. Therefore, we have established a simple method to identify the ALDH2 genotype by analyzing breath samples. Methods: One hundred seven consecutive healthy Japanese volunteers participated in this study. After providing informed consent, participants drank 100 ml of 0.5% ethanol in a single gulp. Breath samples were collected with originally developed simple gasbags before the alcohol was consumed, and 1, 2, and 5 minutes later. The concentrations of acetaldehyde and ethanol in the bag were measured by high-sensitivity gas chromatography. The ALDH2 and ADH1B genotypes of all participants were confirmed using blood DNA. The relationships between acetaldehyde level and genotypes were determined. Results: The frequencies of ALDH2*1/*1, ALDH2*1/*2, and ALDH2*2/*2 were 46.7%, 43.9%, and 9.3%, respectively. The breath acetaldehyde levels at 1 minute after alcohol ingestion were 89.2 (18.1–399.0) ppb in those with ALDH2*1/*1, 346.3 (78.4–1218.4) ppb in those with ALDH2*1/*2, and 537.1 (213.2–1353.8) ppb in those with ALDH2*2/*2. The breath acetaldehyde level was significantly higher in the ALDH2*2 carrier group regardless of the ADH1B genotype (P<0.001). Setting the cutoff for the acetaldehyde/ethanol ratio at 22.3×10 –3 to include ALDH2*2 carriers yielded an accuracy for the detection of ALDH2*2 carriers of 96.3% (95% CI: 91.5–96.9%), sensitivity of 100%, and specificity of 92%. Conclusions: Our breath test may be a convenient screening tool for identifying those at high risk of upper aerodigestive tract cancer.