Association Between Metformin Use and Risk of Esophageal Squamous Cell Carcinoma in a Population-Based Cohort Study

Wang, Qiaoli; Santoni, Giola; Ness-Jensen, Eivind; Lagergren, Jesper; Xie, Shao-Hua

doi:10.14309/ajg.0000000000000478

Cited by 20 publications

(13 citation statements)

References 30 publications

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“…Moreover, the use of metformin was associated with a lower risk of ESCC but not EAC. This result is compatible with those of previous studies [9, 28]. The different effects of metformin on ESCC and EAC may suggest the presence of distinct molecular pathways in these cancer variants, but further studies are required to understand the exact biology.…”

Section: Discussionsupporting

confidence: 92%

“…In another meta-analysis, statins were shown to have a potential chemopreventive effect in both ESCC and EAC [8]. In addition, a population-based cohort study [9] suggested that metformin is associated with a decreased risk of ESCC. However, more comprehensive studies are needed to identify the association between oesophageal cancer and clinical parameters, including medications.…”

Section: Introductionmentioning

confidence: 99%

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Chemoprevention of Oesophageal Squamous-Cell Carcinoma and Adenocarcinoma: A Multicentre Retrospective Cohort Study

et al. 2021

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Background: Oesophageal cancer comprises 2 different histological variants: oesophageal squamous-cell carcinoma (ESCC) and adenocarcinoma (EAC). While there are multiple therapeutic options for both types, patients with advanced or metastatic oesophageal cancer still suffer from poor prognosis. Aims: The study aimed to examine the association between the risk of oesophageal cancer and medications and to estimate the chemopreventive effects of commonly used drugs. Methods: A multicentre retrospective cohort study was conducted using data from 9 hospital databases of hospitalized patients between 2014 and 2019. The primary outcomes were ESCC and EAC. The association of oesophageal cancer with drug use and clinical factors was evaluated. Odds ratios (ORs) were adjusted for age, sex, Charlson comorbidity index scores, and smoking with/without gastro-oesophageal reflux disease. Results: The use of proton pump inhibitors (PPIs) (adjusted OR [aOR] 0.48, p < 0.0001), aspirin (aOR 0.32, p < 0.0001), cyclooxygenase-2 inhibitor (COX2I) (aOR 0.70, p = 0.0005), steroid (aOR 0.19, p < 0.0001), statin (aOR 0.43, p < 0.0001), and metformin (aOR 0.42, p < 0.0001) was associated with a lower risk of ESCC than that in non-use. The use of aspirin (aOR 0.33, p = 0.0006) and steroids (aOR 0.54, p = 0.022) was associated with a lower risk of EAC than that in non-use. Conclusion: COX2Is, statins, metformin, and PPIs could help in prevention of ESCC, and aspirin and steroids may be chemopreventive for both types of oesophageal cancer.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Chemoprevention of Oesophageal Squamous-Cell Carcinoma and Adenocarcinoma: A Multicentre Retrospective Cohort Study

et al. 2021

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“…In addition to the tumors discussed above, the anti-cancer effects of metformin have been demonstrated in other tumors. Wang et al showed in a population-based cohort study that the use of metformin reduced the risk of esophageal cancer and that the effect was significant in new users and the users aged 60-69 years 77 . A regression study showed a negative association between metformin use and the incidence of lung cancer and mortality in lung cancer patients 78 .…”

Section: Clinical Applicationsmentioning

confidence: 99%

Metformin in aging and aging-related diseases: clinical applications and relevant mechanisms

et al. 2022

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Aging is a natural process, which plays a critical role in the pathogenesis of a variety of diseases, i.e., aging-related diseases, such as diabetes, osteoarthritis, Alzheimer disease, cardiovascular diseases, cancers, obesity and other metabolic abnormalities. Metformin, the most widely used antidiabetic drug, has been reported to delay aging and display protective effect on attenuating progression of various aging-related diseases by impacting key hallmark events of aging, including dysregulated nutrient sensing, loss of proteostasis, mitochondrial dysfunction, altered intercellular communication, telomere attrition, genomic instability, epigenetic alterations, stem cell exhaustion and cellular senescence. In this review, we provide updated information and knowledge on applications of metformin in prevention and treatment of aging and aging-related diseases. We focus our discussions on the roles and underlying mechanisms of metformin in modulating aging and treating aging-related diseases.

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“…Several experimental studies have reported that metformin has anti-cancer effects in lung cancer (7), pancreatic cancer (11) and gastric cancer (12) etc. In addition, population-based studies have indicated that metformin use correlated with a reduced incidence rate of various cancers (13)(14)(15)(16). Meanwhile, many primary researches and meta-analyses reported that metformin use was associated with an improved survival outcome in pancreatic cancer (17)(18)(19), lung cancer (20,21), breast cancer (22,23), or colorectal cancer (4), etc.…”

Section: Introductionmentioning

confidence: 99%

The potential adjunctive benefit of adding metformin to standard treatment in inoperable cancer patients: a meta-analysis of randomized controlled trials

Wu¹,

Qu²,

Huang³

et al. 2020

Ann Transl Med

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Background: Recently, there have been several randomized clinical trials (RCTs) conducted to evaluate the efficacy and safety of metformin plus standard treatment in inoperable cancer patients. Our meta-analysis aimed to assess the efficacy of metformin in combination with standard treatment in inoperable cancer patients.Methods: PubMed and Embase databases were systematically searched for relevant RCTs investigating the efficacy of adding metformin to standard treatment for cancer patients. The pooled relative risk (RR) for tumor response and safety was calculated to assess the efficacy of combining metformin with standard treatment. Meta-analysis was subsequently performed to pool the hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS).Results: Ten RCTs comprising 1033 patients were included in our current meta-analysis. In patients with breast cancer, results of meta-analysis showed that the addition of metformin to standard treatment was beneficial to objective response rate (ORR) with 30.3% (33/109) in the metformin plus standard treatment group and 16.1% (18/112) in the placebo group (RR 1.92, 95%

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Association Between Metformin Use and Risk of Esophageal Squamous Cell Carcinoma in a Population-Based Cohort Study

Abstract: Association between metformin use and risk of esophageal squamous cell carcinoma in a populationbased cohort study.

Cited by 20 publications

References 30 publications

Chemoprevention of Oesophageal Squamous-Cell Carcinoma and Adenocarcinoma: A Multicentre Retrospective Cohort Study

Chemoprevention of Oesophageal Squamous-Cell Carcinoma and Adenocarcinoma: A Multicentre Retrospective Cohort Study

Metformin in aging and aging-related diseases: clinical applications and relevant mechanisms

The potential adjunctive benefit of adding metformin to standard treatment in inoperable cancer patients: a meta-analysis of randomized controlled trials

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