The flushing questionnaire may be used in large-scale epidemiological studies as a surrogate marker of ALDH2 genotype to predict individual cancer risk.
The drinking behavior, alcohol-induced facial flushing and ALDH2 genotypes were determined in 283 Thai men comprising 85 who were alcohol-dependent, 62 hazardous/harmful drinkers and 136 non-drinkers or infrequent drinkers.
The ratio of patients who experienced current or former intense vasodilatation upon consuming alcohol (flushing type) was much higher in individuals with the inactive form of ALDH2 encoded by the ALDH2(2)/2(2) or ALDH2(1)/2(2) genotype than in those with the active form of ALDH2 encoded by the ALDH2(1)/2(1) genotype.
The immuno-staining of ALDH2 in the esophageal epithelium was compared with both the drinking habit and the occurrence of flushing that is closely associated with the ALDH2 deficiency.
In the ALDH2(1)/ALDH2(2) group, the frequency of facial flushing with one glass of beer was significantly higher in the ADH2(1)/ADH2(2) and ADH2(2)/ADH2(2) genotype than in the ADH2(1)/ADH2(1) genotype.
Patients with inactive ALDH2, in whom facial flushing is usually observed after the drinking of alcohol, are at high risk for ESCC as well as multiple UADT cancers.
The low sensitivity in the present study suggests that a lack of alcohol flushing may play a crucial role in the development of alcohol dependence in women with inactive ALDH2.
Japanese alcoholic men with (n = 65) and without (n = 206) esophageal squamous cell carcinomas, excluding those with liver cirrhosis, were assessed for MCV within 7 days of their last drink, alone or in combination with findings from either the alcohol flushing questionnaire or genotyping to identify inactive aldehyde dehydrogenase-2 (ALDH2*1/2*2) and the less-active form of alcohol dehydrogenase-2 (ADH2*1/2*1), which pose risks for esophageal squamous cell carcinoma.
Some individuals from the Asian population who carry a mutation in the aldehyde dehydrogenase gene (ALDH2*2) cannot metabolize acetaldehyde as efficiently, producing strong effects, including facial flushing, dizziness, hypotension, and palpitations.
In addition, among the ALDH2-deficient individuals, the atypical homozygote was obviously more hypersensitive to alcohol than the heterozygote, judging from the frequency of flushing or other drinking-associated manifestations with a small dose of alcohol.
The use of simple tests to identify inactive ALDH2 on the basis of alcohol flushing responses could benefit many people, by helping them to identify their own cancer risks.
The mutation in the mitochondrial aldehyde dehydrogenase (ALDH2) gene responsible for alcohol-induced flushing increases turnover of the enzyme tetramers in a dominant fashion.
The first examination of 53 normal volunteers showed that there were differences in the degree of alcohol flushing between the ALDH2 genotypes (P < 0.01).
The Glu504Lys single nucleotide polymorphism (SNP) of ALDH2 gene, which is found in approximately 40% of the East Asian populations, causes defect in the enzyme activity of ALDH2, leading to alterations in acetaldehyde metabolism and alcohol-induced "flushing" syndrome.
The ALDH2*2 allele (A-allele) at rs671 is more commonly carried by Asians and is associated with alcohol-related flushing, a strong adverse reaction to alcohol that is protective against drinking.
The flushing reaction is observed mainly in individuals who possess a mutation in the high-affinity aldehyde dehydrogenase (ALDH2) which renders the enzyme inactive.
However, current regular users of alcohol who reported no alcohol flushing may need to undergo genotyping of ALDH2 for a more accurate assessment of the ALDH2 status.
Significant gene effects were observed for pulse rate and facial flushing (F-values =62.344; p values <0.001 and F-values =7.062; p values =0.010, respectively, by repeated-measures analysis of variance), which were significantly greater in subjects with the ALDH2*1/*2 genotype.
In terms of precision medicine, ~540 million people in the world have a genetic variant of the aldehyde dehydrogenase 2 (ALDH2) enzyme causing a flushing response and tachycardia after alcohol consumption.
The prevalence of alcohol flushing syndrome associated with deficient activity of the variant aldehyde dehydrogenase 2 (ALDH2*2) genotype is prevalent among East Asians.
CAS is prevalent among East Asians and is associated with an aldehyde dehydrogenase 2 (ALDH2)-deficient genotype (ALDH2*2) and alcohol flushing, which is prevalent among East Asians but is virtually non-existent in other populations.
All 3 traits showed genomewide significant association with variants near ALDH2, with significance ranging from 2.01 × 10<sup>-14</sup> (for flushing; lead single nucleotide polymorphism (SNP) PTPN11* rs143894582) to p<sub>meta</sub> = 5.80 × 10<sup>-10</sup> (for alcohol dependence criterion count; lead SNP rs149212747).
We used a questionnaire inquiring about current and past facial flushing after drinking a glass of beer which identifies the presence of inactive ALDH2 with a sensitivity and specificity of approximately 90%.