Does Ranitidine Use Increase Risk of Bladder Cancer?

Does Ranitidine Use Increase Risk of Bladder Cancer?

Vanessa M. Shami, MD, FASGE, reviewing Cardwell CR, et al. Am J Gastroenterol 2021 May 21.

In 2020, the U.S. Food and Drug Administration and other similar bodies recalled all ranitidine products, secondary to a possible increased association with several types of cancers. Although the exact reason for this is unknown, the carcinogen N-nitrosodimethylamine is higher in ranitidine users, especially in their urine. This nested case-control trial using a Scottish database aimed to investigate whether ranitidine use is associated with an increased risk of bladder cancer.

Between 1999 and 2011, bladder cancer cases were identified and matched with up to 5 controls (based on age, sex, general practice, and date of registration). A review of prescribing records identified the use of ranitidine, other histamine-2 receptor agonists, and proton pump inhibitors (PPIs) among patients. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression after adjusting for comorbidities and smoking. 

There were 3260 bladder cancer cases and 14,037 controls that met inclusion criteria. Current or former smoking rates were higher in the bladder cancer group than the control group (26.1% vs 21.0%); however, alcohol use and comorbidities were similar. There was an increased risk of bladder cancer in ranitidine users compared with nonusers (fully adjusted OR, 1.22; 95% CI, 1.06-1.40), which increased with more than 3 years of ranitidine use (fully adjusted OR, 1.43; 95% CI, 1.05-1.94). Conversely, there was little evidence of any association between PPI use and bladder cancer risk based on any ranitidine use (fully adjusted OR, 0.98; 95% CI, 0.88-1.11) or more than 3 years of use (fully adjusted OR, 0.98; 95% CI, 0.80-1.20).

Vanessa M. Shami, MD, FASGE

COMMENT

There is mounting evidence that ranitidine may be associated with a higher risk of bladder cancer. Although the exact mechanism of this association is speculative, further studies such as this one are critical to confirm a causative role and potentially identify high-risk populations.

Note to readers: At the time we reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.

CITATION(S)

Cardwell CR, McDowell RD, Hughes CM, Hicks B, Murchie P. Exposure to ranitidine and risk of bladder cancer: a nested case-control study. Am J Gastroenterol 2021 May 21. (Epub ahead of print) (https://doi.org/10.14309/ajg.0000000000001310)

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