Field Effect of Alcohol, Cigarette Smoking and Their Cessation on the development of Multiple Dysplastic Lesions and Squamous Cell Carcinoma: Long Term Multicenter Cohort Study

Abstract BACKGROUND AND AIMS Multiple development of squamous dysplasia and squamous cell carcinoma (SCC) in the upper aerodigestive tract have been explained by field cancerization phenomenon and was associated with alcohol and cigarette use. Second primary SCC development after curative treatment impairs patients' quality of life and survival, however, how these consumption and cessation affect field cancerization is still unknown. METHODS Multicenter cohort study including 331 superficial esophageal SCC (ESCC) paients treated endoscopically and pooled data from 1,022 healthy subjects for comparison. Physiological condition in the background esophageal mucosa was classified into 3 groups based on the number of Lugol-voiding lesions (LVLs) per endoscopic view: grade A, 0; grade B, 1–9; or grade C, ≥10 LVLs. Lifestyle surveys were conducted using a self-administered questionnaire. Patients were counselled on the need for alcohol and smoking cessation by physicians, and were endoscopically surveyed every 6 months. RESULTS LVL grades were positively associated with alcohol drinking intensity, flushing reactions, smoking, high-temperature food and were negatively with eating green/yellow vegetables and fruit. Second primary ESCC and head/neck SCC were significantly more prevalent in the grade C LVL (cumulative 5-y incidences 47.1%, 95% CI=38.0 to 57.2 and 13.3%, 95% CI=8.1 to 21.5, respectively). Alcohol and smoking cessation significantly reduced the development of second primary ESCC (adjusted hazard ratios 0.47, 95%=CI 0.26 to 0.85 and 0.49, 95% CI=0.26 to 0.91, respectively). CONCLUSIONS Alcohol drinking, smoking, flushing reaction and high-temperature food were closely associated with field cancerization and cessation of alcohol and smoking significantly reduced the risk of development of second primary cancer.