Association of Antihistamine Use with Increased Risk of Esophageal Squamous Cell Carcinoma: A Nationwide, Long-Term Follow-Up Study Using Propensity Score Matching

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.