Excessive drinking is a major risk factor for the development of upper aerodigestive tract cancer (UADTC). As most heavy drinkers smoke and a minority of them (10-20%) develop UADTC, it is thought that constitutional factors predisposing some alcoholics to develop these tumours may play a role. Acetaldehyde appears to be a carcinogenic factor associated with chronic heavy drinking and alcoholics with the ADHIC*1 allele seem to be at particular risk because this allele codes for a rapidly metabolizing enzyme leading to elevated blood acetaldehyde levels. This study investigated for the first time the ADH1C genotype and allele frequency on heavy drinkers with various types of UADTC.
The ADH1C genotype was analysed in 107 Caucasian heavy drinkers with UADTC and 103 alcoholic controls without cancer age-matched to the UADTC group. Both groups had similar mean drinking levels. In addition, alcohol (0.3 g/kg) was administered to 21 healthy volunteers with the ADH1C*1/*1, ADH1C*1/*2 and ADH1C*2/*2 genotypes and to 12 healthy male volunteers with different ADH genotypes who drank alcohol at appetite. Subsequently, salivary acetaldehyde levels were measured.
Results showed that the frequency of the ADHIC*1 allele was higher in the UADTC group than in age-matched alcoholic controls without cancer (61.7% vs. 49.0%). Healthy volunteers with ADHIC*1 allele (ADHIC*1/*1) had higher salivary acetaldehyde levels after alcohol ingestion than healthy volunteers heterozygous for that allele (ADH1C*1/*2) or homozygous for the ADHIC*2 allele (ADHIC*2/*2).
These findings demonstrate that heavy drinkers with the ADHI C*1 /*1 genotype are predisposed to develop upper aerodigestive tract cancer, possibly due to elevated salivary acetaldehyde levels upon alcohol consumption.
Source: Visapää J-P, Götte K, Benesova M et al. Increased cancer risk in heavy drinkers with the alcohol dehyxdrogenase 1C1* alle, possibly due to salivary acetaldehyde . Gut 53(2004) 871-876