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      Is Open Access

      Association between proton pump inhibitor use and the risk of pancreatic cancer: A Korean nationwide cohort study

      research-article
      1 , 2 , 2 , 3 , *
      PLoS ONE
      Public Library of Science

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          Abstract

          Purpose

          Proton pump inhibitor (PPI) therapy causes hypergastrinemia, which could promote the development and progression of pancreatic cancer. Accordingly, this study aimed to investigate the association between PPI exposure and the risk of pancreatic cancer.

          Methods

          We conducted a twelve-year longitudinal population-based study (2002–2013) using the Korean National Health Insurance Corporation claims database merged with national health examination data. The study cohort included 453,655 cancer-free individuals in January 2007 (index date). Incident pancreatic cancer was assessed throughout follow up until December 2013. The exposure to PPIs before the index date was assessed using a standardized Defined Daily Dose (DDD) system. We calculated the hazard ratios (HRs) and their 95% confidence intervals (CIs) for pancreatic cancer risk associated with cumulative PPI use using Cox proportional hazard regression models.

          Results

          There were 3,086 cases of pancreatic cancer during the period of 2,920,000 person-years. PPI users exceeding 60 DDDs were at a higher risk of pancreatic cancer compared with non-users (HR, 1.34; 95% CI, 1.04–1.72). Subgroup analyses revealed that a significant association existed between PPI use and pancreatic cancer in low risk groups including individuals who were female, engaged in healthy lifestyle habits, and had no history of diabetes or chronic pancreatitis.

          Conclusion

          Exposure to PPI appears to increase the risk of pancreatic cancer, independent of conventional risk factors.

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          Most cited references28

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          Problem of immortal time bias in cohort studies: example using statins for preventing progression of diabetes.

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            Pancreatic cancer in chronic pancreatitis; aetiology, incidence, and early detection.

            Acute pancreatitis, chronic pancreatitis and pancreatic cancer are responsible for most of the burden of exocrine pancreatic disease. Glandular damage from recurrent bouts of acute pancreatitis can lead to irreversible changes characteristic of chronic pancreatitis. In recent decades accumulating evidence has defined longstanding pre-existing chronic pancreatitis as a strong risk factor for pancreatic cancer. The lag period between diagnosis of chronic pancreatitis and pancreatic cancer is usually one or two decades: pancreatitis appearing a year or two before the diagnosis of pancreatic cancer is often the result of tumour-related ductal obstruction. The risk of developing pancreatic cancer appears to be highest in rare types of pancreatitis with an early onset, such as hereditary pancreatitis and tropical pancreatitis. Even though there is a strong link between chronic pancreatitis and pancreatic cancer, over a 20 year period only around five percent of patients with chronic pancreatitis will develop pancreatic cancer. Until the development of more sophisticated screening procedures, screening is not recommended for patients with chronic pancreatitis. 2010 Elsevier Ltd. All rights reserved.
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              Risk factors for pancreatic cancer: a summary review of meta-analytical studies.

              The aetiology of pancreatic cancer (PC) has been extensively studied and is the subject of numerous meta-analyses and pooled analyses. We have summarized results from these pooled and meta-analytical studies to estimate the fraction of PCs attributable to each of the identified risk factors.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: MethodologyRole: SupervisionRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: VisualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                12 September 2018
                2018
                : 13
                : 9
                : e0203918
                Affiliations
                [1 ] Department of Family Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea
                [2 ] Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea
                [3 ] Department of Family Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
                Catalan Institute of Oncology, SPAIN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-7498-4829
                Article
                PONE-D-17-27003
                10.1371/journal.pone.0203918
                6135510
                30208110
                4eb2c1f3-2480-4462-a747-08c2e46533f2
                © 2018 Hwang et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 18 July 2017
                : 30 August 2018
                Page count
                Figures: 1, Tables: 3, Pages: 11
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100003725, National Research Foundation of Korea;
                Award ID: 2017R1D1A1B03033721
                Award Recipient :
                This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (grant no. 2017R1D1A1B03033721). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Gastrointestinal Tumors
                Pancreatic Cancer
                Medicine and Health Sciences
                Gastroenterology and Hepatology
                Pancreatitis
                Medicine and Health Sciences
                Diagnostic Medicine
                Cancer Detection and Diagnosis
                Medicine and Health Sciences
                Oncology
                Cancer Detection and Diagnosis
                Medicine and Health Sciences
                Oncology
                Cancer Risk Factors
                Biology and Life Sciences
                Biochemistry
                Hormones
                Peptide Hormones
                Gastrin
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Type 2 Diabetes
                Medicine and Health Sciences
                Metabolic Disorders
                Diabetes Mellitus
                Type 2 Diabetes
                Biology and Life Sciences
                Cell Biology
                Cellular Structures and Organelles
                Cell Membranes
                Membrane Proteins
                Proton Pumps
                Biology and Life Sciences
                Nutrition
                Diet
                Alcohol Consumption
                Medicine and Health Sciences
                Nutrition
                Diet
                Alcohol Consumption
                Custom metadata
                These are third party data. We did not have any special access privileges that others would not have. Anyone can submit a research proposal online ( https://nhiss.nhis.or.kr/bd/ab/bdaba021eng.do). If the proposal is accepted by an evaluation committee of NHIC, researcher would receive the de-identified NHIC dataset after paying some fee.

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                Uncategorized

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