Association Between Long-term Use of H₂ Receptor Antagonists and Prostate Cancer Risk: A Case-Control Study in Taiwan

Objective: The association between long-term use of histamine-2 receptor antagonists and prostate cancer remains unclear. This study aimed to examine the age-specific risk of prostate cancer associated with long-term use of these medications. Methods: We conducted a nationwide case-control study using Taiwan's Health and Welfare Data Science Center database from 2003 to 2016. Men with newly diagnosed prostate cancer were matched to controls, and long-term use was defined as cumulative exposure of sixty days or more. Adjusted odds ratios were estimated using conditional logistic regression, controlling for comorbidities and medications. Results: Among 43,578 prostate cancer cases and 174,312 controls, long-term use of histamine-2 receptor antagonists was associated with a modest increase in prostate cancer risk, significant in men aged sixty-five and older (adjusted odds ratio = 1.087, 95% CI: 1.044-1.131) but not in younger groups. Cimetidine and ranitidine were each associated with increased risk in older men, while famotidine showed no significant association across age groups. Notably, cimetidine uses in men aged forty to sixty-four was associated with reduced prostate cancer risk (adjusted odds ratio = 0.865, 95% CI: 0.755-0.990), suggesting possible age-dependent effects. Conclusions: These findings suggest that long-term use of cimetidine and ranitidine may increase prostate cancer risk in older men, while famotidine was not associated with prostate cancer risk. Risk varies by age and drug type, highlighting the need for drug-specific evaluation in cancer pharmacoepidemiology.