Potentially Causal Associations Between Extensive Gastric Atrophy and Esophageal Squamous Cell Carcinoma: A Nationwide Retrospective Cohort Study in Japan.

Objectives: A potential association between esophageal squamous cell carcinoma (ESCC) and gastric atrophy (GA) has been reported. However, most published studies have used case-control designs, leading to selection bias. This study aimed to investigate the causal association between ESCC and GA using a nationwide cohort.

Methods: A retrospective cohort study was conducted on consecutive participants who underwent endoscopy at 17 health check-up institutes in Japan between 2013 and 2017, with at least one follow-up endoscopy by December 2022. GA was evaluated endoscopically and classified into atrophy-free, closed-type, and open-type GA. The association between ESCC incidence and GA was estimated using the Kaplan-Meier method and Cox regression.

Results: Among 33,461 participants, 17,398 (52.0%), 8257 (24.7%), and 7804 (23.3%) were classified into atrophy-free, closed-type GA, and open-type GA, respectively. Seventy-seven ESCCs were identified during a median 6-year follow-up period. The incidence of ESCC was 24 cases (0.024%/year) in the atrophy-free group, 15 cases (0.031%/year) in the closed-type GA group, and 38 cases (0.089%/year) in the open-type GA group, with a significantly higher incidence observed in the open-type GA group (p < 0.001). After adjusting for established risk factors (e.g., age, sex, drinking, and smoking), open-type GA, but not closed-type GA, was an independent risk factor for ESCC (adjusted hazard ratio: 2.72, 95% confidence interval: 1.58-4.69).

Conclusions: This Japanese nationwide cohort study provides new evidence suggesting a causal association between extensive GA and the subsequent development of ESCC.