ABSTRACT: BACKGROUND:The 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. METHODS:Using 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. RESULTS:DIULs ?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]). CONCLUSIONS:Japanese alcohol-dependent women shared several common risk factors for esophageal squamous cell neoplasia with alcohol-dependent men, but with considerably different magnitudes.
