With knowledge that the carcinogen N-nitrosodimethylamine and increased urinary content of that component in humans, utilizing that drug to investigate whether ranitidine use is associated with increased bladder cancer risk, a nested, case-control study was conducted within the Primary Care Clinical Informatics Unit Research database, containing general practice records from Scotland. Bladder cancer cases, diagnosed between 1999 and 2011 were identified and matched with up to 5 controls, based on age, sex, general practice and date of registration.
Ranitidine, other H2 receptor agonists and proton pump inhibitors were identified from prescribing records. Odds ratios (ORs) and 95% confidence intervals were calculated using conditional logistic regression after adjusting for comorbidities and smoking.
A total of 3260 cases were reviewed with 14,037 controls. There was evidence of increased risk of bladder cancer in ranitidine users, compared with nonusers (OR = 1.22), which was more marked with use over 3 years of ranitidine therapy (OR = 1.43). By contrast, there was little evidence of any association between PPI use and bladder cancer risk, based on any use (OR = 0.98), or over 3 years of use (OR = 0.98).
In this large population-based study, the use of ranitidine, particularly long-term, was associated with an increased risk of bladder cancer.
Cardwell, C., McDowell, R., Hughes, C., et al. “Exposure to Ranitidine and Risk of Bladder Cancer: A Nested, Case-Control Study.” American Journal of Gastroenterology; Vol. 116, August 2021, pp. 1612–1619.