Abstract
Esophageal cancer is a common and aggressive cancer, with a five-year survival rate of approximately 20%. Therefore, identifying safe and effective medications that can reduce the risk of esophageal cancer is of great importance. OBJECTIVE: To examine the association between H1-antihistamines (AHs) use and the incidence of esophageal squamous cell carcinoma (ESCC) in a head-to-head propensity score matching (PSM) comparative study. DESIGN: Retrospective cohort study. SETTING: Nationwide population-based study in Taiwan. PARTICIPANTS: 1289,526 adults from the National Health Insurance Research Database from 2008 to 2018. EXPOSURES: AH use. MAIN OUTCOMES AND MEASURES: Incidence rates (IRs), incidence rate ratios (IRRs), and adjusted hazard ratios (aHRs) of ESCC in AH users compared with nonusers. RESULTS: AH users had a significantly higher IR of ESCC than nonusers (1.47 vs. 1.36 per 100,000 person-years). The IRR (95% CI) for ESCC was 1.18 (1.08-1.28) in AH users compared with nonusers. After adjustment for age, sex, income levels, urbanization, cigarettes smoking, alcoholic related diseases, comorbidities, medication use, and Charlson Comorbidity Index scores, the aHR (95% CI) for ESCC was 1.22 (1.12-1.33) in AH users compared with nonusers. A dose-response relationship was also observed, with aHRs for AH use at 28-182, 183-488, 489-1043, and >1043 cumulative defined daily doses (cDDDs) of 1.12, 1.20, 1.25, and 1.37, respectively, compared with <28 cDDDs. CONCLUSIONS AND RELEVANCE: Our study found a significant association between AH use and the increased risk of ESCC, with a dose-response relationship. This study suggests that AH use may increase the risk of ESCC, especially at high doses, and highlights the importance of caution when prescribing AHs.