Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, PCAM 7S GI, 3400 Civic Center Drive, Philadelphia, PA, 19104, USA.
Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, USA.
Dig Dis Sci. 2022 May;67(5):1822-1830. doi: 10.1007/s10620-021-06972-w. Epub 2021 Apr 15.
The Food and Drug Administration requested withdrawal of ranitidine formulations, due to a potentially carcinogenic contaminant, N-nitrosodimethylamine.
We evaluate whether ranitidine use is associated with gastric cancer.
This is a retrospective multicenter, nationwide cohort study within the Veterans Health Administration, among patients with Helicobacter pylori (HP) prescribed long-term acid suppression with either: (1) ranitidine, (2) other histamine type 2 receptor blocker (H2RB), or (3) proton pump inhibitor (PPI)) between May 1, 1998, and December 31, 2018. Covariates included race, ethnicity, smoking, age, HP treatment, HP eradication. Primary outcome was non-proximal gastric adenocarcinomas, using multivariable Cox proportional hazards analysis.
We identified 279,505 patients with HP prescribed long-term acid suppression (median 53.4 years; 92.9% male). Compared to ranitidine, non-ranitidine H2RB users were more likely to develop cancer (HR 1.83, 95%CI 1.36-2.48); PPI users had no significant difference in future cancer risk (HR 0.92, 95% CI 0.82-1.04), p < 0.001. Demographics associated with future cancer included increasing age (HR 1.18, 95% CI 1.15-1.20, p < 0.001), Hispanic/Latino ethnicity (HR 1.46, 95% CI 1.21-1.75, p < 0.001), Black race (HR 1.89, 95% CI 1.68-2.14) or Asian race (HR 2.03, 95% CI 1.17-3.52), p < 0.001, and gender (female gender HR 0.64, 95% CI 0.48-0.85, p = 0.02). Smoking was associated with future cancer (HR 1.38, 95% CI 1.23-1.54, p < 0.001). Secondary analysis demonstrated decreased cancer risk in those with confirmed HP eradication (HR 0.24, 95% CI 0.14-0.40). No association between ranitidine and increased gastric cancer was found.
There is no demonstrable association between ranitidine use and future gastric cancer among individuals with HP on long-term acid suppression.
由于潜在致癌污染物 N-亚硝基二甲胺，食品和药物管理局要求撤回雷尼替丁制剂。
我们评估雷尼替丁的使用是否与胃癌相关。
这是退伍军人健康管理局内一项回顾性多中心、全国性队列研究，纳入幽门螺杆菌 (HP) 患者，他们接受以下治疗：（1）雷尼替丁，（2）其他组胺 2 型受体阻滞剂 (H2RB) 或（3）质子泵抑制剂 (PPI)，长期酸抑制治疗：（1）雷尼替丁，（2）其他组胺 2 型受体阻滞剂 (H2RB) 或（3）质子泵抑制剂 (PPI)。研究对象为 1998 年 5 月 1 日至 2018 年 12 月 31 日期间接受长期酸抑制治疗的患者。协变量包括种族、民族、吸烟、年龄、HP 治疗、HP 根除。主要结局为非近端胃腺癌，采用多变量 Cox 比例风险分析。
我们确定了 279505 名接受 HP 长期酸抑制治疗的患者（中位年龄 53.4 岁；92.9%为男性）。与雷尼替丁相比，非雷尼替丁 H2RB 使用者发生癌症的风险更高（HR 1.83，95%CI 1.36-2.48）；PPI 使用者未来癌症风险无显著差异（HR 0.92，95%CI 0.82-1.04），p<0.001。与未来癌症相关的人口统计学因素包括年龄增长（HR 1.18，95%CI 1.15-1.20，p<0.001）、西班牙裔/拉丁裔（HR 1.46，95%CI 1.21-1.75，p<0.001）、黑种人（HR 1.89，95%CI 1.68-2.14）或亚洲人（HR 2.03，95%CI 1.17-3.52），p<0.001，以及性别（女性 HR 0.64，95%CI 0.48-0.85，p=0.02）。吸烟与未来癌症相关（HR 1.38，95%CI 1.23-1.54，p<0.001）。二次分析显示，在确认 HP 根除的患者中，癌症风险降低（HR 0.24，95%CI 0.14-0.40）。未发现雷尼替丁与胃癌风险增加之间存在关联。
在接受长期酸抑制治疗的 HP 患者中，雷尼替丁的使用与未来胃癌之间没有明显的关联。
