Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ALDH2”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19Linked to original sources
PubMed2004

Influence of genetic variations of ethanol-metabolizing enzymes on phenotypes of alcohol-related disorders.

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase-2 (ALDH2) play central roles in the metabolism of ethanol and its metabolite, acetaldehyde, in the liver. In ADH2, one nucleotide replacement causes either a super-active beta 2 subunit encoded by the ADH2*2 allele or a less active beta 1 subunit (ADH2*1 allele). In the same way, a G/A replacement at codon 487 of the ALDH2 gene produces an inactive form of the enzyme. Because the geno-types of these genes may explain individual differences in concentration and elimination of ethanol and acetaldehyde in the blood after drinking, they could be used as models to elucidate the contribution of these substances to the development of addiction and various types of organ damage. We have examined the influence of genetic variations of these enzymes on alcohol-related disorders in the Japanese. The results revealed that (1) the less active allele of the ADH2 gene (ADH2*1) is associated with an increased risk for alcohol dependence, alcohol-induced persistent amnestic disorder, alcohol withdrawal syndrome, and cancer of the upper GI tract; (2) the inactive allele of the ALDH2 gene (ALDH2*2) is associated with a decreased risk for alcohol dependence, and an increased risk for alcoholic polyneuropathy and cancer in the same region; and (3) these genetic variations modify clinical features of alcohol dependence. Possible mechanisms of altered risk for these disorders are discussed.

Alcohol Dehydrogenase↗
PubMed1999

Evaluation of the self-rating of the effects of alcohol form in Asian Americans with aldehyde dehydrogenase polymorphisms.

OBJECTIVE: In order to easily assess individual differences in response to alcohol, the Self-Rating of the Effects of Alcohol (SRE) form was recently developed and its psychometric properties tested in primarily white subjects. This study aimed to further evaluate the SRE in a population known to have genetically mediated variability in response to alcohol and risk for alcoholism, Asian Americans with ALDH2 polymorphisms. METHOD: Men and women of Chinese, Japanese or Korean heritage between the ages of 21 and 26 years (N = 156) completed the SRE and a blood sample was drawn for genotyping at the ALDH2 locus. RESULTS: SRE results were available from 137 (78 female) subjects. With the effects of gender, body weight, frequency of recent drinking and quantity of recent drinking controlled, ALDH2 genotype still accounted for a significant amount of variability in SRE score in this Asian-American sample. Evaluation of SRE scores 4.5 or higher indicated that a low response to alcohol was associated with ALDH2*1/2*1 genotype, male gender and Korean heritage, all factors associated with increased risk for alcoholism. CONCLUSIONS: These results provide additional support for the SRE as a valid instrument for assessing individual variability in response to alcohol and as a useful measure for identifying individuals at relatively increased or decreased risk for alcoholism based on level of reaction to alcohol.

Adult↗
PubMed2003

A case-control study of association between life-style, alcohol dehydrogenase 2 and aldehyde dehydrogenase 2 genotype and idiopathic osteonecrosis of the femoral head.

A case-control study of idiopathic osteonecrosis of femoral head (ION) was carried out to investigate the association between workload intensity, smoking, drinking, ADH2 and ALDH2 genotype and other factors and development of ION by comparing 43 cases (34 males and 9 females) without history of systemic corticosteroid use with 86 matched controls (68 males and 18 females). Univariate analysis by conditional logistic regression for males showed statistically significant odds ratios (OR) for heavier workload (OR = 4.661), cumulative alcohol consumption (OR trend per drink-years = 1.015), ALDH2(1/1) (OR = 3.310), consumption of green tea less than 3 or 4 times/week (OR = 2.705), body weight over 60 kg at examination (OR = 0.413), or body mass index of over 25 at examination (OR = 0.208). Multivariate analysis based on a hierarchically well-formulated model strategy for males revealed that heavier workload (OR = 5.785, 95% confidence interval (CI): 1.211, 27.635) and cumulative alcohol consumption (OR = 1.016, 95% CI: 1.005, 1.026) remained as the significantly associated risk factors for ION after adjusting the remaining confounders. The reason for the insignificant multivariate OR of ALDH2(1/1) may be due to the strong confounding of alcohol consumption on the association between ALDH2 genotype and ION. For females, the small sample size made it impossible to produce any meaningful univariate analysis.

Adult↗
PubMed2006

Dysfunction of mitochondria and oxidative stress in the pathogenesis of Alzheimer's disease: on defects in the cytochrome c oxidase complex and aldehyde detoxification.

The mitochondrion is an organelle that plays a central role in energy production. It, at the same time, generates reactive oxygen species as by-products. Large-scale epidemiological case-control studies suggest the involvements of dihydrolipoamide succinyltransferase (DLST) of the mitochondrial Krebs cycle and mitochondrial aldehyde dehydrogenase-2 (ALDH2) in Alzheimer's disease (AD). The DLST gene has two gene-products, one of which, a novel gene product MIRTD, mediates the molecular assembly of the cytochrome c oxidase complex whose defect has been a candidate of the causes of AD. Since levels of MIRTD mRNA in the brains of AD patients were significantly low, a decrease in MIRTD could affect energy production. ALDH2, a matrix enzyme, was found to act as a protector against oxidative stress through oxidizing toxic aldehydes, such as 4-hydroxy-2-nonenal, that are spontaneously produced from lipid peroxides. Hence, a decrease in ALDH2 activity is proposed to contribute to AD. Indeed, transgenic mice with low activity of ALDH2 exhibited an age-dependent neurodegeneration accompanying memory loss. Since amyloid beta peptide has been recently shown to be present in neuronal mitochondria to decline energy production and enhance ROS production, it has become possible to link AD more closely with roles of mitochondria in the pathogenesis.

Alcohol Dehydrogenase↗
PubMed2001

Association between polymorphisms of ethanol-metabolizing enzymes and susceptibility to alcoholic cirrhosis in a Korean male population.

Alcohol is oxidized to acetaldehyde by alcohol dehydrogenase (ADH) and cytochrome P-4502E1 (CYP2E1), and then to acetate by aldehyde dehydrogenase (ALDH). Polymorphisms of these ethanol-metabolizing enzymes may be associated with inter-individual difference in alcohol metabolism and susceptibility to alcoholic liver disease. We determined genotype and allele frequencies of ALDH2, CYP2E1, ADH2, and ADH3 in male Korean patients with alcoholic cirrhosis (n=56), alcoholics without evidence of liver disease (n=52), and nondrinkers (n=64) by using PCR or PCR-directed mutagenesis followed by restriction enzyme digestion. The prevalences of heterozygous ALDH2*1/*2 plus homozygous ALDH2*2/*2 in patients with alcoholic cirrhosis (7.1%) and alcoholics without evidence of liver disease (3.8%) were significantly lower than that in nondrinkers (45.3%). The c2 allele frequencies of the CYP2E1 in alcoholic cirrhosis, alcoholics without evidence of liver disease, and nondrinkers were 0.21, 0.20, and 0.20, respectively. Allele frequencies of ADH2*2 in the three groups were 0.78, 0.74, and 0.77 and those of ADH3*1 were 0.94, 0.98, and 0.95. Therefore, we confirmed the observation that the ALDH2*2 gene protects against the development of alcoholism. However, the development of cirrhosis in Korean alcoholic patients was not associated with polymorphisms of ethanol-metabolizing enzymes.

Adult↗
PubMedDate not supplied

ADH and ALDH polymorphisms among Alaska Natives entering treatment for alcoholism.

The alcohol dehydrogenase (ADHs) and aldehyde dehydrogenases (ALDHs) involved in alcohol metabolism are polymorphic. Different alleles encode subunits of the enzymes that are related to differences in alcohol metabolism with different ethnic groups. This study examined the allele frequencies at the ADH1, ADH2, ADH3 and ALDH2 loci in Alaska Natives entering treatment for alcoholism to determine if allele frequencies at these loci differ among five distinct Alaska Native groups: Yupik and Inupiat Eskimos, Athabascan, Tlingit and Aleut. It was found that all persons were homozygous for the ADH1*1, ADH2*1 and ALDH2*1 alleles. Variations, however, were found for the allele distribution of the ADH3 genotype. Comparison with a general population sample found no differences in allele distributions for ADHs and ALDH2*1, but differences were found when comparisons were made with four Asian Groups. The study's findings suggest that the Alaska Natives are not protected from the risk of alcoholism in the same way that Asians who possess the ALDH2*2 genotype are considered to have a negative risk factor. Nor, does there appear to be any generalized differences between Alaska Native alcoholics and members of the general population with respect to the ALDH and ADH polymorphisms studied herein.

Adolescent↗
PubMed2002

Relationship between genetic polymorphisms of alcohol-metabolizing enzymes and changes in risk factors for coronary heart disease associated with alcohol consumption.

BACKGROUND: There are large individual variations in the responses of risk factors for coronary heart disease to alcohol consumption. To clarify the factors responsible for these individual variations, we studied the relationship between blood pressure, serum lipids, and uric acid and the genetic polymorphisms of alcohol dehydrogenase (ADH) 2 and aldehyde dehydrogenase (ALDH) 2 in alcohol drinkers. METHODS: We examined 133 male workers who drank >300 g of alcohol per week. Information regarding lifestyle habits was obtained by questionnaire. The ADH2 genotype was determined by PCR and subsequent digestion with MaeIII. The ALDH2 genotype was determined based on amplified product length polymorphisms. RESULTS: When the workers were divided into three groups: the ADH2(1)/2(1), ADH2(1)/2(2), and ADH2(2)/2(2) groups, the mean triglycerides and gamma-glutamyl transpeptidase concentrations were significantly higher in the ADH2(2)/2(2) group than in the ADH2(1)/2(1) group. In addition, multiple logistic regression analysis showed that the frequencies of individuals whose systolic blood pressure, triglycerides, and uric acid values were in the highest one third were significantly higher in the ADH2(2)/2(2) group than in the ADH2(1)/2(1) group. In contrast, no difference was observed between the ALDH2(1)/2(1) and (ALDH2(1)/2(2) + ALDH2(2)/2(2)) groups with regard to the mean value of any variable and to the frequency of individuals with any variable value in the highest one third. CONCLUSION: Individuals with the ADH2(1)/2(1) genotype might suffer fewer negative effects of drinking.

Alcohol Dehydrogenase↗
PubMed2002

[Relationship between ethanol patch test and problem drinkers among dental students].

In 2000 and 2001, we carried out a drinking habit survey and the Ethanol Patch Test on 232 fourth-year dental students (128 males, 104 females). The results were statistically analyzed. For the survey, the students were asked to fill out, anonymously, the forms of the Tokyo-University ALDH2-Phenotype Screening Test (TAST), the Kurihama Alcoholism Screening Test (KAST), and the Adolescent Alcohol Involvement Scale (AAIS). The results of the subsequent Ethanol Patch test were evaluated by the students themselves. The Patch test demonstrated that 44.5% of males and 49.0% of females were positive to the test or ALDH2 deficient, the rest having the marker substance. According to the TAST results, ALDH2-deficient or TAST-positive (alcohol-intolerant) subjects accounted for 48.4% of males and 51.9% of females, the rest being ALDH2-present or TAST-negative students. Among the Patch test-positive group, the ratio of problem drinkers according to the KAST was 8.8% in males and 2.0% in females. The corresponding figures for the test-negatives group were; 22.5% in males; 7.5% in females, being higher than those for the test-positive group. Among the test-positive group, the ratio of problem drinkers scoring at least 42 points on the AAIS stood at 19.3% in males, 7.8% in females and among the test-negative group, the corresponding figures were; 21.1% in males; 13.2% in females, the difference from those for the other group being relatively small. The results of the Ethanol Patch test were related to those of the TAST and KAST, but not to the AAIS. The correlation between the Patch test and KAST indicates that the test-negatives are prone to become alcohol-dependant. Though the results of the Patch test and those of the AAIS were not related, the findings show that some alcohol-intolerant university students are drinking excessively.

Adult↗
PubMed2003

Polymorphisms for vinyl chloride metabolism in French vinyl chloride workers.

Genetic polymorphisms of aldehyde dehydrogenase 2 (ALDH2) and cytochrome P450 2E1 (CYP2E1) have been shown to influence the degree of genetic damage in Taiwanese workers exposed to the carcinogen - vinyl chloride(VC). Certain French VC workers have been found to express biomarkers of mutant forms of cancer-related proteins (ras-p21 and p53) that have been related to their exposure. ALDH2 and CYP2E1 polymorphisms were investigated in 211 of these workers in an attempt to correlate differences in VC metabolic capacity with differences in the presence of these biomarkers. All of the workers were found to have the normal, wild-type ALDH2 gene, and none of them were found to be homozygous for the variant CYP2E1 allele. Sixteen workers were found to be heterozygous for the variant CYP2E1 allele. After adjusting for age, smoking, drinking and cumulative VC exposure, the odds ratio for the presence of either the mutant ras-p21 or the mutant p53 biomarker in these heterozygous workers was found to be statistically significantly increased in comparison to their homozygous, wild-type counterparts (OR = 5.05; 95% CI = 1.10-23.25). However, as opposed to the case in Taiwanese workers, these polymorphisms are relatively uncommon, and thus differences in ALDH2 and CYP2E1 can account for only a small proportion of the variability in mutagenic response to VC exposure in a Caucasian population.

Adult↗
PubMedDate not supplied

[Alcoholism-related genetic alteration].

AIMS: A number of studies about human genetics have shown how inheritance is involved in a predisposition towards alcohol abuse or towards developing alcoholism. Similarly, molecular genetics researchers have drawn attention to the importance of the enzymatic systems that metabolize ethanol and acetaldehyde in the study of alcoholism. These systems are essentially alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), although the roles played by cytochrome P450 2E1 and catalase are notable. DEVELOPMENT: The existence of a functional polymorphism in some of the genes that codify for these enzymes could generate an alteration in the acetaldehyde synthesis interval or lower the extent to which it is later oxidized. A selection of this genetic polymorphism might act in certain human populations, such as the oriental population, as a factor that protects against alcohol abuse and the damage and injuries associated with this drug. CONCLUSION: Subjects with a sensitivity to alcohol that is genetically controlled by the abnormality contained in their allele for ALDH2*2 would present some kind of protection against excessive consumption of alcohol. Moreover, subjects with a heterozygotic genotype of ALDH2*2 (ALDH2*1/2*2) would present a greater risk of developing injuries and damage in the organs related to alcohol abuse as compared to subjects who present a homozygotic genotype of ALDH2*1/2*1.

Alcohol Dehydrogenase↗
PubMed2005

Change of components of the metabolic syndrome in a workers' health checkup after five years--relation with elevated liver enzymes, gene polymorphisms for ALDH 2, beta3-AR and lifestyle.

We previously reported that the prevalence of elevated alanine aminotransferase (ALT) increases with accumulation of metabolic syndrome components, and a greater degree of involvement of aldehyde dehydrogenase 2 (ALDH2) than beta3-adrenergic receptor gene (beta3-AR) polymorphisms. The present study was designed to clarify the effect of aging, lifestyle and the two gene polymorphisms on the relationship between 4 components of the metabolic syndrome (obesity, hypertension, dyslipidemia and impaired glucose tolerance) and elevated ALT values in a subset of 73 out of 148 male workers who were 35 years of age in the baseline study and 40 years old in the present study. Study subjects completed questionnaires about drinking and smoking habits, and underwent urinalysis, physical examination and peripheral blood tests, blood chemistry, electrocardiogram and chest X-rays each year as required by Japanese law. Information from the questionnaires and physical examinations, including liver function tests, were compared with previously reported ALDH2 and beta3-AR genotypes for the 73 workers. Of the 73 workers studied, 14 (19%) demonstrated decrease in metabolic syndrome components, 39 (53%) demonstrated no change, and 20 (27%) demonstrated an increase. Ten workers (14%) showed liver dysfunction at age 35 and 20 workers (27%) at age 40. Fourteen workers were newly diagnosed as having liver dysfunction at their 40-year checkup, thus being associated with the BMI and an active ALDH2 genotype. Accumulation of components of the metabolic syndrome were associated with the presence of liver dysfunction at 35 years. In conclusion, these findings indicate that ALDH2 genotyping as well as lifestyle habits may be important factors in causing metabolic syndrome with liver dysfunction.

Adult↗
PubMed2006

[Polymorphisms of aldehyde and alcohol dehydrogenase genes associated with susceptibility to trichloroethylene-induced medicamentosa-like dermatitis].

OBJECTIVE: Investigate the genetic polymorphisms of aldehyde dehydrogenase (ALDH) and alcohol dehydrogenase (ADH), major enzymes involving the trichloroethylene (TCE) metabolism, associated with susceptibility to TCE-induced medicamentosa-like dermatitis. METHODS: The study included 108 patients with TCE-induced medicamentosa-like dermatitis and 145 healthy controls exposed to TCE who were engaged in the same workplace, and frequency matched by sex and age. The genotypes of ADH2, ADH3 and ALDH2 were analyzed by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP), and distribution of genotype and odds ratio were calculated. RESULTS: There were no differences in the frequencies of genotypes of ADH2 and ADH3 between cases and exposed controls. The frequency of heterozygous ALDH2 * 1/ * 2 plus homozygous ALDH2 * 2/ * 2 in cases was significantly lower than that in exposed controls (27.8% vs 43.4%, P = 0.011), and it decreased the risk of TCE-induced medicamentosa-like dermatitis (OR = 0.50, 95% CI = 0.29-0.85). CONCLUSION: The active ALDH2 might be one of the factors influencing the individual susceptibility to TCE-induced medicamentosa-like dermatitis.

Adolescent↗
PubMed1986

Chromosomal assignment of the genes for human aldehyde dehydrogenase-1 and aldehyde dehydrogenase-2.

Chromosomal assignment of the genes for two major human aldehyde dehydrogenase isozymes, that is, cytosolic aldehyde dehydrogenase-1 (ALDH1) and mitochondrial aldehyde dehydrogenase-2 (ALDH2) were determined. Genomic DNA, isolated from a panel of mouse-human and Chinese hamster-human hybrid cell lines, was digested by restriction endonucleases and subjected to Southern blot hybridization using cDNA probes for ALDH1 and for ALDH2. Based on the distribution pattern of ALDH1 and ALDH2 in cell hybrids, ALDH1 was assigned to the long arm of human chromosome 9 and ALDH2 to chromosome 12.

Aldehyde Dehydrogenase↗
PubMed1995

Characterization of diethyldithiocarbamate methyl ester sulfine as an intermediate in the bioactivation of disulfiram.

Disulfiram is bioactivated through a series of intermediates, ultimately forming S-methyl-N,N-diethylthiolcarbamate sulfoxide (DETC-Me sulfoxide), the metabolite proposed to be responsible for the in vivo inhibition of rat liver mitochondrial low Km aldehyde dehydrogenase (ALDH2). Diethyldithiocarbamate methyl ester sulfine (DDTC-Me sulfine) also has been recently identified as a possible metabolite of disulfiram (Madan and Faiman, 1994). In the present studies, DDTC-Me sulfine was characterized and was found to inhibit ALDH2 in vivo (ID50 = 57 mumol/kg) but not in vitro. Maximum inhibition of ALDH2 in rats was observed 1 hr after the i.p. administration of DDTC-Me sulfine. Pretreatment of rats with 1-benzylimidazole, a cytochrome P450 inhibitor, blocked the DDTC-Me sulfine-mediated inhibition of ALDH2. This suggested that DDTC-Me sulfine was further bioactivated by a cytochrome P450-dependent mechanism. DDTC-Me sulfine could not be detected in rat plasma after the i.p. administration of disulfiram (75 mg/kg), DDTC-Me (122 mg/kg) or DDTC-Me sulfine (22.6 mg/kg). However, S-methyl N,N-diethylthiolcarbamate (DETC-Me), the desulfurated form of DDTC-Me, was detected as a major metabolite of DDTC-Me sulfine in rat plasma after DDTC-Me sulfine administration. Also, a disulfiram-like-ethanol reaction was observed in rats treated with DDTC-Me sulfine and challenged with ethanol. These data provided additional support for the idea that DDTC-Me sulfine is an intermediate formed after DDTC-Me metabolism and is probably a precursor to DETC-Me in the overall bioactivation of disulfiram to DETC-Me sulfoxide.

Aldehyde Dehydrogenase↗
PubMed1994

Polymorphism of alcohol and aldehyde dehydrogenase genes and alcoholic cirrhosis in Chinese patients.

Liver alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), the principal enzymes responsible for the oxidation of ethanol, are polymorphic at the ADH2, ADH3 and ALDH2 loci in human beings. Our previous studies have shown that, compared with nonalcoholic individuals, Chinese alcoholic patients without liver disease had significantly lower frequencies of the ADH2*2 and ADH3*1 alleles, which encode high maximum velocity beta 2- and gamma 1-ADH subunits, respectively, as well as a lower frequency of the ALDH2*2 allele, which encodes an enzymatically inactive subunit. The data strongly suggest that genetic variation in both ADH and ALDH may influence drinking behavior and the risk of alcoholism developing through acetaldehyde formation. To further investigate the possible role of acetaldehyde in the pathogenesis of alcoholic liver disease, we determined the ADH and ALDH genotype frequencies in patients with alcohol-related cirrhosis (n = 27), viral hepatitis-related cirrhosis (n = 29) and gastric and duodenal ulcer without relevance to alcohol (n = 30). We developed a new restriction fragment length polymorphism method to genotype the mutant and normal ALDH2 alleles by using polymerase chain reaction-directed mutagenesis, which proved to be simpler and faster than the conventional detection methods that use hybridization with allele-specific oligonucleotide probes. We found that the frequencies of the alleles ADH2*2 (57%), ADH3*1 (78%) and ALDH2*2 (9%) in the alcoholic cirrhotic patients were significantly lower than those in the healthy controls and in the patients with cirrhosis from viral hepatitis and with gastric and duodenal ulcer.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Dehydrogenase↗
PubMed1995

Alcohol flushing, patch test, and ADH and ALDH genotypes in Brazilian ethnic groups.

Self reports of flushing reaction after drinking, cutaneous sensitivity to alcohol (patch test), and genotypic determination of ADH2, ADH3, and ALDH2 were studied in 53 Brazilian volunteers of different ethnic groups. Genotypes were determined using single-strand conformation polymorphism in discontinuous buffer electrophoresis. Analysis of the results indicated several cases of a reported flushing reaction among ALDH2 1/1 individuals, while all but 2 cases of ALDH2 heterozygotes reported a flushing reaction. The latter subjects also had a negative result in the patch test. These preliminary results indicate that variability in the facial flushing reaction to alcohol seems to be a phenomenon resulting not only from the presence of a deficient ALDH2*2 allele, but also from other polymorphisms of alcohol-metabolizing enzymes.

Adult↗
PubMed1996

Mitochondrial ALDH polymorphism affects ethanol-derived acetate disposition in Wistar rats.

We studied the relationship between polymorphism of aldehyde dehydrogenase (ALDH) and ethanol and acetate kinetics in male Wistar rats. Blood ethanol and acetate concentration time curves after intravenous bolus administration of 1 g/kg of ethanol were estimated by moment analysis. ALDH isozymes in hepatic subcellular fractions were detected by isoelectric focusing (IEF). Blood acetate profiles were divided into two patterns: one-peak type and two-peak type. IEF studies on ALDH isozymes in subcellular fractions showed polymorphism of cytosolic and mitochondrial ALDHs. Polymorphism patterns of ALDH2 corresponded with patterns of blood acetate profiles. Significant differences in mean residence time of acetate and the ratio of area under curves (AUCs) of acetate to ethanol (AUCacetate/AUCEtOH) occurred between different IEF patterns of mitochondrial low K(m) ALDH (ALDH2). Therefore, it was clarified that ALDH2 polymorphism affects ethanol-derived acetate disposition in Wistar rats. Similarity of AUC values of acetate considered, these observations suggest that ALDH2 polymorphism results in change of effects of acetate and acetate-generated adenosine on the central nervous system and other organs during chronic ethanol consumption.

Acetaldehyde↗
PubMed1998

Short-term follow-up after endoscopic mucosectomy of early esophageal cancer and aldehyde dehydrogenase-2 genotype in Japanese alcoholics.

The risk of the future development of primary esophageal cancer after endoscopic esophageal mucosal resection of esophageal cancer is not known; hence, there are no established guidelines for follow-up surveillance programs. Simultaneous occurrence of multiple cancers associated with esophageal cancer is common among heavy drinkers who have the inactive form of aldehyde dehydrogenase-2 (ALDH2) as a risk factor. Thirty-four Japanese male alcoholics with intraepithelial or mucosal squamous cell carcinoma in the esophagus were treated by endoscopic esophageal mucosal resection, followed by endoscopy and esophageal iodine staining, to find the additional development of primary esophageal cancer. Primary esophageal squamous cell carcinoma was detected in nine patients (26.5%) at 3-21 months after the first cancer diagnosis. Cancer occurred more frequently in patients with inactive ALDH2 than it did in those with active ALDH2 [42.1% (8 of 19) versus 6.7% (1 of 15), P = 0.047], and it occurred more frequently in those with multiple esophageal cancers than it did in those without them [60.0% (6 of 10) versus 12.5% (3 of 24), P = 0.009]. Kaplan-Meier estimates of the proportions of patients with additional primary esophageal cancers showed that patients with inactive ALDH2 (P = 0.024) or multiple esophageal cancers (P = 0.007) had a significantly increased likelihood of the development of additional cancer. Close follow-up examinations using endoscopy and iodine staining are needed for such high-risk patients.

Adult↗