The Effect of Alcohol, Cigarette Smoking and Their Cessation for Risk of Field Cancerization of Esophagus and Head and Neck

Background: Multiple development of dysplastic squamous epithelium and squamous cell carcinoma (SCC) in the esophagus and head/neck region was associated with alcohol and cigarette use and have been explained by field cancerization phenomenon. Second primary cancer developed after curative treatment have harmful effect on patients’ quality of life and survival, however, until recently there have been no evidence-based assessment of the effects of these consumption and cessation on field cancerization.  Methods: We conducted a multicentre cohort study at 16 hospitals in Japan. Patients with superficial esophageal SCC (ESCCs) who treated by endoscopic resection were registered. Dysplastic squamous epithelium in the background esophageal mucosa was evaluated by Lugol chromoendoscopy and 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, ³10 LVLs. Lifestyle surveys were conducted using a self-administered questionnaire. Patients were counselled on the need for ceasing alcohol and cigarette consumption by physicians, and were evaluated endoscopical surveillance every 6 months. This study conforms to the STROBE guidelines Findings: Between September 12, 2005 and April 9, 2010, 331 patients with superficial ESCCs were registered. Pooled data from 1,022 healthy subjects were used for comparison. Grades of LVL were positively associated with alcohol drinking intensity, flushing reactions, smoking, high-temperature food and negatively with eating green/yellow vegetables and fruit. Secondary ESCCs and HNSCCs were significantly more prevalent in the grade C LVL group (cumulative 5-y incidences 47.1%, 95% confidence interval [CI], 38.0 to 57.2, and 13.3%, 95% CI, 8.1 to 21.5, respectively). Ceasing alcohol and cigarette use significantly reduced the development of secondary ESCCs (adjusted hazard ratios 0.47, 95% CI, 0.26 to 0.85 and 0.49, 95% CI, 0.26 to 0.91, respectively) Interpretation: Alcohol and cigarette use were closely associated with field cancerization and cessation of them significantly reduced the risk of development of second primary cancer. Funding Statement: Grant from National Cancer Center Research and Development Fund 36 by the Ministry of Health, Labour and Welfare of Japan. Declaration of Interests: The authors declared no conflict of interest. Ethics Approval Statement: This study was approved by the institutional review board at each hospital, and we obtained written informed consent from all patients. (UMIN Clinical Trials Registry ID:UMIN000001676).