Increased salivary acetaldehyde levels in heavy drinkers and smokers: a microbiological approach to oral cavity cancer

Abstract

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.

Removal of acetaldehyde from saliva by a slow‐release buccal tablet of L‐cysteine

“…19 Furthermore, in vitro acetaldehyde production by mouthwashings from oropharyngolaryngeal cancer patients has been shown to be significantly higher than that of the control patients, 11 and the production of acetaldehyde in saliva from ethanol is markedly increased in smokers and heavy drinkers. 38 To prevent the harmful effects of ethanol-derived acetaldehyde, beside being an abstainer, we show that two-thirds of acetaldehyde can be trapped in the saliva with slowly and continuously released L-cysteine. Thiol compounds, such as cysteine, are known to be able to protect against acetaldehyde toxicity.…”

“…38 Moreover, poor oral hygiene, heavy alcohol drinking and smoking may contribute to the individual risk of upper GI-tract cancers by increasing the acetaldehyde levels in the oral cavity. 38 Our buccal drug formulation slowly releases cysteine to the oral cavity. Thus, it enables a continuous concentration of cysteine in the mouth during microbially mediated ethanol oxidation and acetaldehyde challenge.…”

Characterization of oral microbiota and acetaldehyde production

“…In particular, increased ACH levels in saliva have been associated with increased risk for upper aerodigestive tract cancer [3–5], which was the seventh most common cancer in Japan in 2011 with one million newly diagnosed cases annually worldwide [6,7]. Increased ACH levels in saliva after ethanol consumption are suggested to be due to oxidation of alcohol by the oral microbiota [8,9]. …”

Chronic candidosis and oral cancer in APECED‐patients: Production of carcinogenic acetaldehyde from glucose and ethanol by Candida albicans

“…[10][11][12] They all associate with increased acetaldehyde (ACH) levels in saliva, and there is strong evidence supporting the role of ACH as a common dominator. [13][14][15][16][17][18] The mechanism leading to increased ACH levels in saliva after alcohol consumption is local microbial ACH production, i.e. the oxidation of salivary ethanol (EtOH) to ACH by microbial alcohol dehydrogenase (ADH)-enzyme.…”

“…the oxidation of salivary ethanol (EtOH) to ACH by microbial alcohol dehydrogenase (ADH)-enzyme. [15][16][17] Previous studies have shown that Candida albicans can produce significant amounts of carcinogenic ACH in clinically relevant EtOH concentrations. 19 It has been demonstrated that polyamines are able to facilitate the formation of mutagenic DNA-adducts in biologically relevant ACH concentrations (50-100 lM).…”