Dataset Information

Telomere shortening in the esophagus of Japanese alcoholics: relationships with chromoendoscopic findings, ALDH2 and ADH1B genotypes and smoking history.

ABSTRACT: Chromoendoscopy with Lugol iodine staining provides important information on the development of squamous cell carcinoma (SCC). In particular, distinct iodine-unstained lesions (DIULs) larger than 10 mm show a high prevalence in high-grade intraepithelial neoplasia. It has also been reported that inactive ALDH2*1/*2 and less-active ADH1B*1/*1, and smoking, are risk factors for esophageal SCC. We previously examined telomere shortening in the esophageal epithelium of alcoholics, and suggested a high prevalence of chromosomal instability in such individuals. In the present study, we attempted to analyze telomere lengths in 52 DIULs with reference to both their size and multiplicity, ALDH2 and ADH1B genotypes, and smoking history. Patients with DIULs <10 mm (n?=?42) had significantly longer telomeres than those with DIULs ?10 mm (n?=?10, p?=?0.008). No significant differences in telomere length were recognized between the ALDH2 and ADH1B genotypes (ALDH2 active/inactive?=?35/17, ADH1B active/inactive?=?32/20; p?=?0.563, 0.784, respectively) or among four groups of patients divided according to smoking history (never-, ex-, light, and heavy smokers?=?3, 6, 21, and 22 patients, respectively; p?=?0.956). Patients without multiple DIULs (n?=?17) had significantly longer telomeres than patients with multiple DIULs (n?=?35, p?=?0.040). It is suggested that alcoholism reduces telomere length in the esophagus, irrespective of genotype or smoking habit. Telomere shortening may not generate cancer directly, but may create conditions under which SCC can develop more easily, depending on subsequent exposure to carcinogens.

SUBMITTER: Aida J

PROVIDER: S-EPMC3646776 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Telomere shortening in the esophagus of Japanese alcoholics: relationships with chromoendoscopic findings, ALDH2 and ADH1B genotypes and smoking history.

Aida Junko J Yokoyama Akira A Shimomura Naotaka N Nakamura Ken-ichi K Ishikawa Naoshi N Terai Masanori M Poon Steven S Matsuura Masaaki M Fujiwara Mutsunori M Sawabe Motoji M Arai Tomio T Takubo Kaiyo K

PloS one 20130507 5

Chromoendoscopy with Lugol iodine staining provides important information on the development of squamous cell carcinoma (SCC). In particular, distinct iodine-unstained lesions (DIULs) larger than 10 mm show a high prevalence in high-grade intraepithelial neoplasia. It has also been reported that inactive ALDH2*1/*2 and less-active ADH1B*1/*1, and smoking, are risk factors for esophageal SCC. We previously examined telomere shortening in the esophageal epithelium of alcoholics, and suggested a hi ...[more]

PMID: 23667679

Similar Datasets

Project description:BackgroundThe presence of large or multiple esophageal distinct iodine-unstained lesions (DIULs) is a strong predictor of field cancerization in the upper aerodigestive tract. Several risk factors for DIULs, including genetic polymorphisms of alcohol and aldehyde dehydrogenases (ADH1B, rs1229984; ALDH2, rs671), have been demonstrated in Japanese alcohol-dependent men. However, few evaluations of alcohol-dependent women have been conducted in this field.MethodsUsing multiple logistic regression models, we investigated the results of screening using esophageal iodine staining and the identification of determinants for esophageal DIULs in 472 Japanese alcohol-dependent women.ResultsDIULs ≥5 mm, multiple DILUs, and both characteristics were observed in 35 (7.4%), 31 (6.6%), and 16 (3.4%) patients, respectively. DIULs ≥5 mm were histologically diagnosed as low-grade intraepithelial neoplasia in 26 patients and superficial squamous cell carcinoma in 9 patients. Although the inactive heterozygous ALDH2*1/*2 genotype was more common (33.3% vs. 11.4%, p = 0.002) in the group with DIULs ≥5 mm than in the group without DIULs ≥5 mm, no significant differences in the results of a questionnaire asking about current and past facial flushing after a glass of beer were seen between the groups with and without DIULs ≥5 mm. When individuals with current or former flushing were assumed to have inactive ALDH2, the sensitivity and specificity of current or former flushing to identify the presence of inactive ALDH2 were 50.0% and 93.5%, respectively; these values were previously reported to be 88% and 92%, respectively, in a Japanese general female population. 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. No significant differences in age, usual alcohol consumption, or smoking habits were observed according to ADH1B and ALDH2 genotypes. Multiple logistic regression analyses showed that the slow-metabolizing ADH1B*1/*1 genotype (odds ratio [95% confidence interval], 12.5 [4.82-32.4] and 9.89 [3.50-27.9]), the inactive heterozygous ALDH2*1/*2 genotype (2.94 [1.18-7.38] and 3.79 [1.40-10.3]), a lower body mass index per -1 kg/m2 (1.17 [1.02-1.35] and 1.38 [1.14-1.67]), and a mean corpuscular volume ≥106 fl (3.70 [1.56-8.81] and 3.27 [1.24-8.64]) increased the risk of DIULs ≥5 mm and multiple DIULs, respectively. The combination of ADH1B*1/*1 and ALDH2*1/*2 markedly increased the risk of esophageal DIULs ≥5 mm (39.3 [10.6-146]).ConclusionsJapanese alcohol-dependent women shared several common risk factors for esophageal squamous cell neoplasia with alcohol-dependent men, but with considerably different magnitudes.

Project description:The length of telomeres located at the ends of chromosomes has attracted attention as an indicator of cellular and individual aging. Various diseases or stresses cause telomere shortening, and it has been reported that alcohol use disorder patients actually have shorter telomeres than healthy patients. However, the factors that contribute to the reduction in telomere length among alcohol use disorder patients have not been clarified in detail. Therefore, in this study, we explored the factors that reduce telomere length in alcohol use disorder patients. A questionnaire survey and a measurement of leukocyte telomere length were conducted among alcohol use disorder patients. The mean telomere length of leukocyte was measured by ∆∆Ct analysis using a real-time PCR. We compared the telomere length between alcohol use disorder patients and the control group (Japanese special health check-up examinee). Moreover, we searched for factors associated with telomere length from drinking/smoking characteristics and history of comorbidities. A total of 74 subjects had alcohol use disorder, and 68 were in the control group. Compared to the control group, alcohol use disorder patients had significantly shorter telomere lengths (p < 0.001). A multivariate analysis revealed that a longer duration of smoking resulted in a significantly shorter telomere length (p = 0.0129). In addition, a comparison of the telomere length between the groups with and without a history of suffering from each disease revealed that telomere length was significantly shorter in the group with diabetes than in the group without diabetes (p = 0.0371). This study reveals that in individuals with alcohol dependence, particularly, prolonged smoking habits and the presence of diabetes contribute to telomere shortening. Medication and support for abstinence from alcohol has been mainly provided for alcohol use disorder patients. Our findings demonstrate a potential support approach via smoking cessation programs and controlling diabetes, which may be helpful to suppress the shortening of healthy life expectancy among alcohol use disorder patients.

Dataset Information

Telomere shortening in the esophagus of Japanese alcoholics: relationships with chromoendoscopic findings, ALDH2 and ADH1B genotypes and smoking history.

Publications

Telomere shortening in the esophagus of Japanese alcoholics: relationships with chromoendoscopic findings, ALDH2 and ADH1B genotypes and smoking history.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets