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Pharmacoepidemiological Research on N-Nitrosodimethylamine-Contaminated Ranitidine Use and Long-Term Cancer Risk: A Population-Based Longitudinal Cohort Study

Author

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  • Chun-Hsiang Wang

    (Department of Hepatogastroenterology, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan 701033, Taiwan
    Department of Optometry, Chung Hwa Medical University, Tainan 701033, Taiwan)

  • I-I Chen

    (Department of Hepatogastroenterology, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan 701033, Taiwan
    These author contributed equally to this work.)

  • Chung-Hung Chen

    (Department of Gastroenterology, Chang Bing Show Chwan Memorial Hopital, Changhua 505029, Taiwan
    These author contributed equally to this work.)

  • Yuan-Tsung Tseng

    (Committee of Medical Research, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan 701033, Taiwan)

Abstract

N-Nitrosodimethylamine (NDMA), a carcinogenic chemical, has recently been identified in ranitidine. We conducted a population-based study to explore ranitidine use and cancer emergence over time. Using the Taiwan National Health Insurance Research Database, a population-based cohort study was conducted. A total of 55,110 eligible patients who received ranitidine between January 2000 and December 2018 were enrolled in the treated cohort. We conducted a 1:1 propensity-score-matching procedure to match the ranitidine-treated group with the ranitidine-untreated group and famotidine controls for a longitudinal study. The association of ranitidine exposure with cancer outcomes was assessed. A multivariable Cox regression analysis that compared cancer risk with the untreated groups revealed that ranitidine increased the risk of liver (hazard ratio (HR): 1.22, 95% confidence interval (CI): 1.09–1.36, p < 0.001), lung (HR: 1.17, CI: 1.05–1.31, p = 0.005), gastric (HR: 1.26, CI: 1.05–1.52, p = 0.012), and pancreatic cancers (HR 1.35, CI: 1.03–1.77, p = 0.030). Our real-world observational study strongly supports the pathogenic role of NDMA contamination, given that long-term ranitidine use is associated with a higher likelihood of liver cancer development in ranitidine users compared with the control groups of non-ranitidine users treated with famotidine or proton-pump inhibitors.

Suggested Citation

  • Chun-Hsiang Wang & I-I Chen & Chung-Hung Chen & Yuan-Tsung Tseng, 2022. "Pharmacoepidemiological Research on N-Nitrosodimethylamine-Contaminated Ranitidine Use and Long-Term Cancer Risk: A Population-Based Longitudinal Cohort Study," IJERPH, MDPI, vol. 19(19), pages 1-16, September.
    • Handle: RePEc:gam:jijerp:v:19:y:2022:i:19:p:12469-:d:929935
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    References listed on IDEAS

    as
    1. Peikes, Deborah N. & Moreno, Lorenzo & Orzol, Sean Michael, 2008. "Propensity Score Matching: A Note of Caution for Evaluators of Social Programs," The American Statistician, American Statistical Association, vol. 62, pages 222-231, August.
    2. Alberto Abadie & Jann Spiess, 2022. "Robust Post-Matching Inference," Journal of the American Statistical Association, Taylor & Francis Journals, vol. 117(538), pages 983-995, April.
    3. Masao Iwagami & Ryosuke Kumazawa & Yoshihisa Miyamoto & Yuri Ito & Miho Ishimaru & Kojiro Morita & Shota Hamada & Nanako Tamiya & Hideo Yasunaga, 2021. "Risk of Cancer in Association with Ranitidine and Nizatidine vs Other H2 Blockers: Analysis of the Japan Medical Data Center Claims Database 2005–2018," Drug Safety, Springer, vol. 44(3), pages 361-371, March.
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