Katada C, Muto M, Tanabe S, Higuchi K, Sasaki T, Azuma M, Ishido K, Katada N, Sakuramoto S, Yamashita K, Masaki T, Nakayama M, Okamoto M, Koizumi W
Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan.
Dis Esophagus. 2014 Jul;27(5):457-62. doi: 10.1111/j.1442-2050.2012.01429.x. Epub 2012 Sep 25.
Multicentric squamous dysplasia of the esophagus is characterized by multiple Lugol-voiding lesions (LVLs) on Lugol chromoendoscopy. Multiple LVLs are associated with a very high risk of multiple cancers arising in the esophagus as well as the head and neck. To gain insight into the pathogenesis of multiple LVLs of the esophageal mucosa, we studied risk factors for the development of such lesions in 76 patients who had a current or previous diagnosis of esophageal squamous cell carcinoma. All patients underwent Lugol chromoendoscopy of the esophageal mucosa. The history of tobacco and alcohol use was documented. Polymorphisms of the aldehyde dehydrogenase type 2 (ALDH2) gene were identified by polymerase chain reaction using sequence-specific primers. Clinical factors related to multiple LVLs were analyzed. All patients with multiple LVLs were drinkers. On univariate analysis, male sex (odds ratio [OR] 15, 95% confidence interval [CI] 1.84-122.45: P = 0.011), presence of the ALDH2-2 allele (OR 4.5, 95% CI 1.55-13.24: P = 0.006), and smoking index ≥1000 (OR 2.6, 95% CI 1.02-6.6: P = 0.045) were associated with multiple LVLs. On multivariate analysis, male sex (OR 10.02, 95% CI 1.13-88.44: P = 0.038) and presence of the ALDH2-2 allele (OR 4.56, 95% CI 1.4-14.82: P = 0.012) were associated with multiple LVLs. Among drinkers, a daily alcohol intake of ≥100 g pure ethanol with the ALDH2-2 allele (OR 17.5, 95% CI 1.97-155.59: P = 0.01) and a daily alcohol intake of <100 g pure ethanol with the ALDH2-2 allele (OR 8.85, 95% CI 1.68-46.69: P = 0.01) more strongly correlated with multiple LVLs than did a daily alcohol intake of <100 g pure ethanol without the ALDH2-2 allele, whereas a daily alcohol intake of ≥100 g pure ethanol without the ALDH2-2 allele (OR 4.0, 95% CI 0.54-29.81: P = 0.18) did not. In conclusion, male sex and the ALDH2-2 allele are associated with an increased risk for multiple LVLs of the esophageal mucosa in patients with esophageal squamous cell carcinoma. Among drinkers with the ALDH2-2 allele, the risk of multiple LVLs increased in parallel to the daily alcohol intake.
食管多中心鳞状发育异常的特征是在卢戈氏染色内镜检查时出现多个不染卢戈氏碘的病变（LVLs）。多个LVLs与食管以及头颈部发生多处癌症的极高风险相关。为深入了解食管黏膜多个LVLs的发病机制，我们研究了76例目前或既往诊断为食管鳞状细胞癌患者发生此类病变的危险因素。所有患者均接受了食管黏膜的卢戈氏染色内镜检查。记录了烟草和酒精使用史。使用序列特异性引物通过聚合酶链反应鉴定乙醛脱氢酶2型（ALDH2）基因的多态性。分析了与多个LVLs相关的临床因素。所有有多个LVLs的患者均为饮酒者。单因素分析显示，男性（优势比[OR]15，95%置信区间[CI]1.84 - 122.45：P = 0.011）、存在ALDH2 - 2等位基因（OR 4.5，95%CI 1.55 - 13.24：P = 0.006）以及吸烟指数≥1000（OR 2.6，95%CI 1.02 - 6.6：P = 0.045）与多个LVLs相关。多因素分析显示，男性（OR 10.02，95%CI 1.13 - 88.44：P = 0.038）和存在ALDH2 - 2等位基因（OR 4.56，95%CI 1.4 - 14.82：P = 0.012）与多个LVLs相关。在饮酒者中，每日纯乙醇摄入量≥100g且携带ALDH2 - 2等位基因（OR 17.5，95%CI 1.97 - 155.59：P = 0.01）以及每日纯乙醇摄入量<100g且携带ALDH2 - 2等位基因（OR 8.85，95%CI 1.68 - 46.69：P = 0.01）与多个LVLs的相关性比每日纯乙醇摄入量<100g且不携带ALDH2 - 2等位基因更强，而每日纯乙醇摄入量≥100g且不携带ALDH2 - 2等位基因（OR 4.0，95%CI 0.54 - 29.81：P = 0.18）则不然。总之，男性和ALDH2 - 2等位基因与食管鳞状细胞癌患者食管黏膜多个LVLs的风险增加相关。在携带ALDH2 - 2等位基因的饮酒者中，多个LVLs的风险随每日酒精摄入量平行增加。
