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      Metformin use and risk of gastric adenocarcinoma in a Swedish population-based cohort study

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          Abstract

          Background

          Whether or not the use of metformin decreases the risk of gastric adenocarcinoma is unclear.

          Methods

          This was a population-based cohort study in 2005–2015. Associations between metformin use and gastric non-cardia and cardia adenocarcinomas were examined within two cohorts; a diabetes cohort of participants using anti-diabetes medications, and a matched cohort of common-medication users, where metformin non-users were frequency matched (10:1) with metformin users for sex and age. Multivariable Cox proportional hazard regression analyses provided hazard ratios (HR) and 95% confidence intervals (CI), adjusting for sex, age, calendar year, comorbidity, Helicobacter pylori eradication treatment, use of non-steroidal anti-inflammatory drugs or aspirin and use of statins.

          Results

          During the follow-up for a median of 5.8 years, 892 (0.1%) participants in the diabetes cohort and 6395 (0.1%) participants in the matched cohort of common-medication users developed gastric adenocarcinoma. Metformin users had no significantly decreased risk of gastric non-cardia adenocarcinoma (diabetes cohort: HR 0.93, 95% CI 0.78–1.12; matched cohort: HR 1.30, 95% CI 1.18–1.42) or cardia adenocarcinoma (diabetes cohort: HR 1.49, 95% CI 1.09–2.02; matched cohort: HR 1.58, 95% CI 1.38–1.81) compared with non-users in both cohorts.

          Conclusions

          This cohort study with <10 years of follow-up suggests metformin use may not prevent gastric adenocarcinoma.

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          Most cited references31

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          Fasting serum glucose level and cancer risk in Korean men and women.

          Diabetes is a serious and costly disease that is becoming increasingly common in many countries. The role of diabetes as a cancer risk factor remains unclear. To examine the relationship between fasting serum glucose and diabetes and risk of all cancers and specific cancers in men and women in Korea. Ten-year prospective cohort study of 1,298,385 Koreans (829,770 men and 468,615 women) aged 30 to 95 years who received health insurance from the National Health Insurance Corp and had a biennial medical evaluation in 1992-1995 (with follow-up for up to 10 years). Death from cancer and registry-documented incident cancer or hospital admission for cancer. During the 10 years of follow-up, there were 20,566 cancer deaths in men and 5907 cancer deaths in women. Using Cox proportional hazards models and controlling for smoking and alcohol use, the stratum with the highest fasting serum glucose (> or =140 mg/dL [> or =7.8 mmol/L]) had higher death rates from all cancers combined (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.22-1.37 in men and HR, 1.23; 95% CI, 1.09-1.39 in women) compared with the stratum with the lowest level (<90 mg/dL [<5.0 mmol/L]). By cancer site, the association was strongest for pancreatic cancer, comparing the highest and lowest strata in men (HR, 1.91; 95% CI, 1.52-2.41) and in women (HR, 2.05; 95% CI, 1.43-2.93). Significant associations were also found for cancers of the esophagus, liver, and colon/rectum in men and of the liver and cervix in women, and there were significant trends with glucose level for cancers of the esophagus, colon/rectum, liver, pancreas, and bile duct in men and of the liver and pancreas in women. Of the 26,473 total cancer deaths in men and women, 848 were estimated as attributable to having a fasting serum glucose level of less than 90 mg/dL. For cancer incidence, the general patterns reflected those found for mortality. For persons with a diagnosis of diabetes or a fasting serum glucose level greater than 125 mg/dL (6.9 mmol/L), risks for cancer incidence and mortality were generally elevated compared with those without diabetes. In Korea, elevated fasting serum glucose levels and a diagnosis of diabetes are independent risk factors for several major cancers, and the risk tends to increase with an increased level of fasting serum glucose.
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            Changing Trends in Stomach Cancer Throughout the World.

            The paper aims to discuss the global trends in gastric cancer incidence in relation to important factors involved in the pathogenesis of gastric cancer.
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              The First Decade with the Swedish Prescribed Drug Register - A Systematic Review of the Output in the Scientific Literature.

              The aim of this study was to quantify and characterize the scientific output from the Swedish Prescribed Drug Register (SPDR) the first decade after its establishment. A systematic literature search was performed in Medline, EMBASE and PubMed (2005-2014). Additional publications were identified by personal knowledge, reference lists, contact with active authors and a citation search in Web of Sciences. Publications using SPDR data were included in the analysis and characterized regarding study type, presence of patient-level record linkage, target population and topic. A total of 719 publications were identified in the literature search and an additional 148 by other strategies. Three hundred and thirty-eight studies fulfilled the inclusion criteria. The majority were analytic (n = 166; 49.1%) or descriptive (n = 100; 29.5%). The remaining studies focused on validation (n = 20; 5.9%), health economics (n = 16; 4.7%) or miscellaneous (n = 36; 10.7%). The analytic studies investigating effects of drug exposure focused mainly on safety (n = 46) and/or effectiveness (n = 24). The first publications appeared in 2007 (n = 6), and in 2014, 90 articles using SPDR were published. Over the years, linkage with other registers using the personal identity number increased (0-88.9% of the publications). The population was often selected by age (49.7%), condition (45.0%) and/or drug (22.8%) and concerned predominantly psychiatric (29.0%) and cardiovascular (20.4%) diseases. In conclusion, this study illustrates that the establishment of a nationwide individual-based register on dispensed prescription drugs facilitates an encouraging development of pharmacoepidemiological research, both regarding the number of publications and the scientific level of the analyses.
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                Author and article information

                Contributors
                +46 8 517 70917 , shaohua.xie@ki.se
                Journal
                Br J Cancer
                Br. J. Cancer
                British Journal of Cancer
                Nature Publishing Group UK (London )
                0007-0920
                1532-1827
                8 October 2019
                12 November 2019
                : 121
                : 10
                : 877-882
                Affiliations
                [1 ]ISNI 0000 0000 9241 5705, GRID grid.24381.3c, Upper Gastrointestinal Surgery, Department of Molecular medicine and Surgery, Karolinska Institutet, , Karolinska University Hospital, ; Stockholm, Sweden
                [2 ]ISNI 0000 0001 2322 6764, GRID grid.13097.3c, School of Cancer and Pharmaceutical Sciences, , King’s College London, ; London, UK
                Article
                598
                10.1038/s41416-019-0598-z
                6889304
                31591459
                6822116b-f187-4250-aacc-f705002e64b5
                © The Author(s), under exclusive licence to Cancer Research UK 2019

                This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).

                History
                : 1 July 2019
                : 17 September 2019
                : 19 September 2019
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100004359, Vetenskapsrådet (Swedish Research Council);
                Award ID: SIMSAM D0547801
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100002794, Cancerfonden (Swedish Cancer Society);
                Award ID: CAN 2015/460
                Award Recipient :
                Categories
                Article
                Custom metadata
                © Cancer Research UK 2019

                Oncology & Radiotherapy
                cancer epidemiology,gastric cancer,cancer prevention,epidemiology
                Oncology & Radiotherapy
                cancer epidemiology, gastric cancer, cancer prevention, epidemiology

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