Shria Kumar1, David S Goldberg2, David E Kaplan3,4. 1. Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, PCAM 7S GI, 3400 Civic Center Drive, Philadelphia, PA, 19104, USA. shriakumar@gmail.com. 2. Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, USA. 3. Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, PCAM 7S GI, 3400 Civic Center Drive, Philadelphia, PA, 19104, USA. 4. Division of Gastroenterology, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, USA.
Abstract
BACKGROUND: The Food and Drug Administration requested withdrawal of ranitidine formulations, due to a potentially carcinogenic contaminant, N-nitrosodimethylamine. AIMS: We evaluate whether ranitidine use is associated with gastric cancer. METHODS: 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. RESULTS: 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. CONCLUSION: There is no demonstrable association between ranitidine use and future gastric cancer among individuals with HP on long-term acid suppression.
BACKGROUND: The Food and Drug Administration requested withdrawal of ranitidine formulations, due to a potentially carcinogenic contaminant, N-nitrosodimethylamine. AIMS: We evaluate whether ranitidine use is associated with gastric cancer. METHODS: 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. RESULTS: 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. CONCLUSION: There is no demonstrable association between ranitidine use and future gastric cancer among individuals with HP on long-term acid suppression.
Authors: Paul Moayyedi; Sander J O Veldhuyzen van Zanten; Lawrence Hookey; David Armstrong; Nicola Jones; Grigorios I Leontiadis Journal: Gut Date: 2018-07-13 Impact factor: 23.059