Sa286 PROTON PUMP INHIBITION INCREASES RISK FOR PANCREATIC CARCINOGENESIS

Huber, Matthew; Nadella, Sandeep; Cao, Hong; Kallakury, Bhaskar; Tucker, Robin D.; Gay, Martha D.; Shivapurkar, Narayan; Edmondson, Elijah F.; Yue, Yuanzhen; Fang, Hong-Bin; Smith, Jill P.

doi:10.1016/s0016-5085(21)01829-1

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“…[17] According to Matthew A Huber et al, hypergastrinemia resulting from PPIs could be the cause of pancreatic intraepithelial neoplasia and pancreatic malignancies, and this hypothesis was confirmed through animal experiments. [18] PPIs might increase the risk of digestive system tumor occurrence by elevating blood gastrin concentration, increasing nitrite concentration, and enhancing the toxicity of chemotherapy drugs. Conversely, PPIs could act as a protective factor for digestive system tumors by modifying the tumor microenvironment, regulating tumor cell pH value, promoting tumor cell apoptosis, inhibiting tumor cell growth, improving tumor cell drug resistance, and other functions.…”

Section: Discussionmentioning

confidence: 99%

Does proton pump inhibitors use increase risk of digestive tumors?: A 2-sample Mendelian randomization study

Zhao,

Lin,

Han

et al. 2023

Medicine

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The objective of this study was to explore the causal relationship between the use of proton pump inhibitors (PPIs) and 16 types of digestive system tumors. We utilized a 2-sample Mendelian randomization (MR) approach to investigate this relationship. We obtained exposure and outcome data from the UK Biobank and the Finland Biobank, respectively. The genetic data used in the analysis were derived from genome-wide association studies (GWAS) studies conducted on European populations. We screened single nucleotide polymorphisms significantly associated with the use of omeprazole, a commonly used PPIs, as instrumental variables. We then performed MR analyses using the inverse variance weighting (IVW) method, MR-Egger regression, and the weighted median method to evaluate the causal effect of omeprazole use on the 16 types of digestive system tumors. Our MR analysis revealed a significant causal relationship between the use of omeprazole and pancreatic malignancies, but not with any other types of digestive system tumors. The IVW analysis showed an odds ratio of 4.33E-05 (95%CI: [4.87E-09, 0.38], P = .03) and the MR-Egger analysis showed an odds ratio of 5.81E-11 (95%CI: [2.82E-20, 0.12], P = .04). We found no significant heterogeneity or pleiotropy, and sensitivity analysis confirmed the robustness of our results. Furthermore, statistical power calculations suggested that our findings were reliable. Conclusion The use of PPIs is a protective factor for pancreatic malignancies, but no causal relationship has been found with other digestive system tumors.

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Section: Discussionmentioning

confidence: 99%