Chronic ethanol ingestion leads to an enhanced risk of upper gastrointestinal tract cancer. Although many hypotheses for the tumor promoting effect of alcohol exist, the pathogenetic mechanisms remain unclear since alcohol in itself is not carcinogenic. Acetaldehyde, the first metabolite of ethanol, has been shown to have multiple mutagenic effects and to be carcinogenic to animals. Previous research has revealed that acetaldehyde can be formed from ethanol via microbial alcohol dehydrogenase. Thus, at least part of the proposed tumorigenic effect of ethanol may be linked to local production of acetaldehyde from ethanol by oral microflora. In this study we demonstrate the production of marked amounts of acetaldehyde in saliva after ingestion of moderate amounts of ethanol. Considerable inter individual variation in acetaldehyde production capacity is also shown. In vivo acetaldehyde production is significantly reduced after a 3-day use of an antiseptic mouthwash (chlorhexidine). In vitro acetaldehyde production was shown to be linear in time, inhibited by 4-methylpyrazole and it could not be saturated under ethanol conditions that are relevant in vivo. There was a significant positive correlation between salivary acetaldehyde production in vitro and in vivo. We conclude, that the microbial formation of acetaldehyde in saliva could be one explanation for the tumor promoting effect of ethanol on the upper gastrointestinal tract. Moreover, this may support the epidemiological finding, that poor oral hygiene is an independent risk factor for oral cavity cancer.

The pathogenetic mechanisms behind alcohol-associated carcinogenesis in the upper digestive tract remain unclear, as alcohol is not carcinogenic. However, there is increasing evidence that a major part of the tumour-promoting action of alcohol might be mediated via its first, toxic and carcinogenic metabolite acetaldehyde. Acetaldehyde is produced from ethanol in the epithelia by mucosal alcohol dehydrogenases, but much higher levels derive from microbial oxidation of ethanol by the oral microflora. In this study we investigated factors that might alter the composition and quantities of the oral microflora and, consequently, influence microbial acetaldehyde production. Information about dental health, smoking habits, alcohol consumption and other factors was obtained by a questionnaire from 326 volunteers with varying social backgrounds and health status, e.g. oral cavity malignancy. Paraffin-induced saliva was collected and the microbial production of acetaldehyde from ethanol was measured. Smoking and heavy drinking were the strongest factors increasing microbial acetaldehyde production. Whether poor dental status may alter local acetaldehyde production from ethanol remained unanswered. Bacterial analysis revealed that mainly gram-positive aerobic bacteria and yeasts were associated with higher acetaldehyde production. Increased local microbial salivary acetaldehyde production due to ethanol among smokers and heavy drinkers could be a biological explanation for the observed synergistic carcinogenic action of alcohol and smoking on upper gastrointestinal tract cancer. It offers a new microbiological approach to ethanol-associated carcinogenesis at these anatomic sites.

Background and aimsAtrophic gastritis (AG) results most often from Helicobacter pylori (H. pylori) infection. AG is the most important single risk condition for gastric cancer that often leads to an acid-free or hypochlorhydric stomach. In the present paper, we suggest a rationale for noninvasive screening of AG with stomach-specific biomarkers.MethodsThe paper summarizes a set of data on application of the biomarkers and describes how the test results could be interpreted in practice.ResultsIn AG of the gastric corpus and fundus, the plasma levels of pepsinogen I and/or the pepsinogen I/pepsinogen II ratio are always low. The fasting level of gastrin-17 is high in AG limited to the corpus and fundus, but low or non-elevated if the AG occurs in both antrum and corpus. A low fasting level of G-17 is a sign of antral AG or indicates high intragastric acidity. Differentiation between antral AG and high intragastric acidity can be done by assaying the plasma G-17 before and after protein stimulation, or before and after administration of the proton pump inhibitors (PPI). Amidated G-17 will rise if the antral mucosa is normal in structure. H. pylori antibodies are a reliable indicator of helicobacter infection, even in patients with AG and hypochlorhydria.ConclusionsStomach-specific biomarkers provide information about the stomach health and about the function of stomach mucosa and are a noninvasive tool for diagnosis and screening of AG and acid-free stomach.

Alcohol drinking and smoking are independent risk factors for upper digestive tract cancers. Furthermore, their combined use interacts in a multiplicative way on cancer risk. There is convincing evidence that acetaldehyde, the first metabolite of ethanol and a constituent of tobacco smoke, is a local carcinogen in humans. Therefore, we examined the combined effect of alcohol drinking and tobacco smoking on in vivo acetaldehyde concentration in saliva. Seven smokers and 6 nonsmokers participated in the study. First, to measure the effect of alcohol on salivary acetaldehyde, all volunteers ingested 0.8 g/kg body weight of ethanol and saliva samples were collected every 20 min for 160 min thereafter. After a 3-day washout period, smokers ingested again the same amount of ethanol and smoked one cigarette every 20 min and saliva samples were collected at 10 min intervals for 160 min. Acetaldehyde and ethanol concentrations were analyzed by headspace gas chromatograph. Firstly, smokers without concomitant smoking during ethanol challenge had 2 times higher in vivo salivary acetaldehyde concentrations than nonsmokers after ethanol ingestion (AUC 114. The main causes of upper digestive tract cancers are smoking and alcohol drinking. It has been estimated, for the United States, that up to 80% of these cancers can be avoided by abstaining from alcohol drinking and smoking. 1-3 Both alcohol and tobacco are independent risk factors for upper digestive tract cancers. Additionally, several epidemiologic studies have confirmed that alcohol and tobacco interact in a multiplicative way on cancer risk. 4 -8 The combined tumor-promoting effect of alcohol and tobacco smoking is poorly understood. Ethanol per se is not carcinogenic. 9 However, acetaldehyde, the first metabolite of ethanol, is carcinogenic in animals. 10,11 There is convincing evidence for acetaldehyde being the ultimate carcinogenic compound behind alcohol intake also in humans. 12,13 After alcohol intake, acetaldehyde is locally formed in the oral cavity by oral mucosal alcohol dehydrogenases (ADHs) and by the oral microflora, both of which are able to oxidize ethanol to acetaldehyde. 14 -16 Also, tobacco smoke contains high levels of acetaldehyde, which is one of the most toxic compounds in cigarette smoke condensate. 17 Acetaldehyde is highly toxic and mutagenic under various experimental conditions. 18 -21 Epidemiologic and biochemical studies on Asian heavy drinkers with aldehyde dehydrogenase-2 (ALDH2) deficiency strongly suggest that acetaldehyde is a local and topical carcinogen also in humans. 13 This deficiency results in the accumulation of acetaldehyde in saliva 22 and in markedly increased risk for upper gastrointestinal (GI) tract cancers. [23][24][25] Also, most studies concerning Caucasian individuals who are homozygous for the fast alcohol metabolizing alcohol dehydrogenase (ADH3*1) enzyme show increased salivary acetaldehyde levels related to increased risk of alcohol-related upper digestive tract cancers. 26 Our earlier studies indicate that he...