Objective: The risk of alcohol dependence (AD) in Japanese men and women was evaluated according to combinations of alcohol flushing andaldehyde dehydrogenase-2(ALDH2, rs671) andalcohol dehydrogenase-1B(ADH1B, rs1229984) genotypes, all of which are known to determine AD susceptibility in Asians. Previous studies have focused on men, since women account for a smaller proportion of AD subjects.Methods: Case control studies were conducted between 3721 male and 335 female AD Japanese and 610 male and 406 female controls who were asked about their current or former tendency to experience facial flushing after drinking a glass of beer and underwentALDH2andADH1Bgenotyping. The time at which alcohol-induced facial flushing tendencies had disappeared in former-flushing AD subjects was also evaluated.Results: Current alcohol flushing, the inactiveALDH2*1/*2genotype, and the fast-metabolizingADH1B*2allele were less frequently found in the AD groups. Although alcohol flushing was strongly influenced by theALDH2andADH1Bgenotypes, multiple logistic model showed that never or former flushing and the genotype combinations were independent strong risk factors of AD in men and women. Never or former flushing (vs. current flushing) markedly increased the odds ratios of AD in carriers of each of theALDH2andADH1Bgenotype combinations. The temporal profiles for drinking and flushing in former-flushing AD subjects revealed that the flushing response disappeared soon after or before the start of habitual drinking during young adulthood, regardless of theALDH2genotype.Conclusion: Although alcohol flushing is influenced by theALDH2andADH1Bgenotypes, constitutional or acquired flushing tolerance is an independent susceptibility trait for AD. The combination of the alcohol flushing status and theALDH2andADH1Bgenotypes can provide a better new strategy for AD risk assessment than the alcohol flushing status alone or the genotypes alone in Asian men and women.

Background: Digital health technologies using mobile apps and wearable devices are a promising approach to the investigation of substance use in the real world and for the analysis of predictive factors or harms from substance use. Moreover, consecutive repeated data collection enables the development of predictive algorithms for substance use by machine learning methods. Objective: We developed a new self-monitoring mobile app to record daily substance use, triggers, and cravings. Additionally, a wearable activity tracker (Fitbit) was used to collect objective biological and behavioral data before, during, and after substance use. This study aims to describe a model using machine learning methods to determine substance use. Methods: This study is an ongoing observational study using a Fitbit and a self-monitoring app. Participants of this study were people with health risks due to alcohol or methamphetamine use. They were required to record their daily substance use and related factors on the self-monitoring app and to always wear a Fitbit for 8 weeks, which collected the following data: (1) heart rate per minute, (2) sleep duration per day, (3) sleep stages per day, (4) the number of steps per day, and (5) the amount of physical activity per day. Fitbit data will first be visualized for data analysis to confirm typical Fitbit data patterns for individual users. Next, machine learning and statistical analysis methods will be performed to create a detection model for substance use based on the combined Fitbit and self-monitoring data. The model will be tested based on 5-fold cross-validation, and further preprocessing and machine learning methods will be conducted based on the preliminary results. The usability and feasibility of this approach will also be evaluated. Results: Enrollment for the trial began in September 2020, and the data collection finished in April 2021. In total, 13 people with methamphetamine use disorder and 36 with alcohol problems participated in this study. The severity of methamphetamine or alcohol use disorder assessed by the Drug Abuse Screening Test-10 or the Alcohol Use Disorders Identification Test-10 was moderate to severe. The anticipated results of this study include understanding the physiological and behavioral data before, during, and after alcohol or methamphetamine use and identifying individual patterns of behavior. Conclusions: Real-time data on daily life among people with substance use problems were collected in this study. This new approach to data collection might be helpful because of its high confidentiality and convenience. The findings of this study will provide data to support the development of interventions to reduce alcohol and methamphetamine use and associated negative consequences. International Registered Report Identifier (IRRID): DERR1-10.2196/44275

BACKGROUND Multiple intraesophageal primary cancer and upper aerodigestive tract (UADT) cancer associated with esophageal cancer are common diseases, especially in heavy drinkers. They are often explained by the concept of field cancerization, which suggests a similar etiology. However, little is known about the nature of the hypothesized etiology. METHODS Among 901 Japanese male alcoholics systematically screened by upper gastrointestinal endoscopy (with esophageal iodine staining), 33 had squamous cell carcinoma of the esophagus. The multiplicity of their esophageal carcinoma and their concurrent UADT cancer was compared with their genotype for aldehyde dehydrogenase‐2 (ALDH2), the major determinant of blood acetaldehyde concentration after drinking. RESULTS Of 17 patients with inactive ALDH2, 13 (76.5%) had multiple primary carcinoma of the esophagus, whereas 5 of 16 (31.3%) with active ALDH2 had multiple carcinomas (P < 0.01). The prevalence of concurrent UADT cancer was 29.4% in those patients with inactive ALDH2, compared with 6.3% in those patients with active ALDH2. CONCLUSIONS Inactive ALDH2 is a risk factor for multiple carcinoma of the esophagus in alcoholics. Acetaldehyde, a recognized animal carcinogen, appears to play a critical role in field cancerization. Cancer 1996;77:1986‐90.

Aim: To test for the possible association between mitochondrial aldehyde dehydrogenase (ALDH2) promoter polymorphism and alcoholism. Methods: Genotyping to identify the polymorphisms in 515 alcoholic patients and 361 normal controls was performed. Results: There were no significant differences between the genotype and allele frequencies of the −357A/G polymorphism in alcoholics and normal controls. Linkage disequilibrium was observed between the promoter and exon 12 polymorphisms. Conclusion: These results suggest the ALDH2 promoter polymorphism does not affect the risk for alcoholism.