McGwin Gerald
Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL 35223, USA.
Cancers (Basel). 2020 Dec 23;13(1):24. doi: 10.3390/cancers13010024.
N-nitrosodimethylamine (NDMA) is a carcinogen in experimental animals. It has been classified a probable human carcinogen and has been found in ranitidine. This study sought to evaluate the association between ranitidine use and cancer of the gastrointestinal system. Events reported to the FDA Adverse Events Reporting System that were associated with the use of proton pump inhibitors (PPIs) and H antagonists were selected. Proportionate reporting ratios (PRRs) and associated 95% confidence intervals (CIs) were calculated to compare the proportion of all reported adverse events that were for gastrointestinal system cancers among adverse event reports for ranitidine to adverse event reports for other H antagonists. The proportion of adverse events for any gastrointestinal system cancer relative to all other events was elevated for ranitidine compared to PPIs and other H antagonists (PRR 3.66, 95% CI 3.19-4.20). Elevated and significant PRRs were observed for pharyngeal (PRR 9.24), esophageal (PRR 3.56), stomach (PRR 1.48), colorectal (PRR 16.31), liver (PRR 2.64), and pancreatic (PRR 2.18) cancers. The PRRs for anal (PRR 4.62) and gallbladder (PRR 4.62) cancer were also elevated though not statistically significant. In conjunction with a large body of epidemiologic and human and animal basic science research, the study results support the hypothesis that NDMA-contaminated ranitidine increases the risk of cancer and supports the withdrawal of these medications from the market.
N-亚硝基二甲胺（NDMA）在实验动物中是一种致癌物。它已被归类为可能的人类致癌物，并且已在雷尼替丁中被发现。本研究旨在评估雷尼替丁的使用与胃肠道系统癌症之间的关联。选择了向美国食品药品监督管理局不良事件报告系统报告的与使用质子泵抑制剂（PPI）和H拮抗剂相关的事件。计算比例报告率（PRR）和相关的95%置信区间（CI），以比较雷尼替丁不良事件报告中胃肠道系统癌症的所有报告不良事件比例与其他H拮抗剂不良事件报告中的比例。与PPI和其他H拮抗剂相比，雷尼替丁的任何胃肠道系统癌症不良事件相对于所有其他事件的比例有所升高（PRR 3.66，95% CI 3.19 - 4.20）。观察到咽癌（PRR 9.24）、食管癌（PRR 3.56）、胃癌（PRR 1.48）、结直肠癌（PRR 16.31）、肝癌（PRR 2.64）和胰腺癌（PRR 2.18）的PRR升高且具有统计学意义。肛门癌（PRR 4.62）和胆囊癌（PRR 4.62）的PRR也有所升高，尽管无统计学意义。结合大量的流行病学以及人类和动物基础科学研究，研究结果支持以下假设：受NDMA污染的雷尼替丁会增加癌症风险，并支持将这些药物从市场上撤下。
