Clinicopathological features of esophageal squamous cell carcinoma in never smoker-never drinkers

Most individuals with esophageal squamous cell carcinoma (ESCC) have a history of tobacco smoking and/or excessive alcohol consumption, which are established risk factors for this disease. However, a minority of patients have no history of exposure to these risk factors, and their disease etiology remains unclear. The aim of this study is to determine the clinicopathological features of ESCC patients in never smoker-never drinkers. Consecutive ESCC patients who underwent esophagectomy between 2005 and 2013 (N = 691) were retrospectively analyzed. The nonsmoking and nondrinking (NSND) group consisted of patients with no habitual exposure to either smoking or drinking, while the smoking or drinking (SD) group comprised of those who had engaged in one or both activities. Clinicopathological parameters as well as survival rates were compared between the groups. The NSND group included only 30 patients (4.3%). Compared with the SD group, the NSND group included more women and a higher proportion of individuals with a family history of esophageal cancer. The incidence of multiple lesions was significantly lower in the NSND group, while the rate of well-differentiated tumors was higher than the SD group. The stepwise regression analysis revealed that female gender, advanced age, well-differentiated histology, and presence of family history of esophageal cancer were the significant features of ESCC in the NSND group. Differences in the clinicopathologic features between the groups were observed only in women but not in men. Five of 22 women (22.7%) in the NSND group had family histories of esophageal cancer in their first-degree relatives. Survival rates were comparable between the groups. ESCC among women in the NSND group demonstrated clinicopathologic features that significantly differed from typical alcohol-or smoking-induced ESCC. Family histories of esophageal cancer were frequently observed in these patients, suggesting that they are genetically predisposed to carcinogenesis.