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

Abstract

<b><i>Background:</i></b> 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. <b><i>Aims:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> The use of proton pump inhibitors (PPIs) (adjusted OR [aOR] 0.48, <i>p</i> < 0.0001), aspirin (aOR 0.32, <i>p</i> < 0.0001), cyclooxygenase-2 inhibitor (COX2I) (aOR 0.70, <i>p</i> = 0.0005), steroid (aOR 0.19, <i>p</i> < 0.0001), statin (aOR 0.43, <i>p</i> < 0.0001), and metformin (aOR 0.42, <i>p</i> < 0.0001) was associated with a lower risk of ESCC than that in non-use. The use of aspirin (aOR 0.33, <i>p</i> = 0.0006) and steroids (aOR 0.54, <i>p</i> = 0.022) was associated with a lower risk of EAC than that in non-use. <b><i>Conclusion:</i></b> COX2Is, statins, metformin, and PPIs could help in prevention of ESCC, and aspirin and steroids may be chemopreventive for both types of oesophageal cancer.

Assessment of the Relationship Between Gastric-Acid Suppressants and the Risk of Esophageal Adenocarcinoma: A Systematic Review and Meta-Analysis

“…28 Finally, 20 articles were selected for the final evaluation to investigate the association between gastric acid suppressants and the risk of developing EAC. 9 , 10 , 11 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 …”

“…From the 20 studies in this analysis, there were 1,155,699 patients. Of these, 11 studies used a cohort design, which included 1,125,437 patients 10 , 11 , 29 , 30 , 31 , 34 , 35 , 38 , 39 , 42 , 45 and 8 studies had a case–control design, with 27,727 participants. 9 , 32 , 33 , 36 , 40 , 41 , 43 , 44 One study was conducted as an randomized controlled trial and included 2,535 patients.…”

“… 10 , 32 , 34 , 39 , 40 , 42 , 43 , 44 , 45 Two studies were from Asia (eg, Japan and South Korea) and involved 312,848 participants. 11 , 29 Eight studies included 804,032 participants from Europe (eg, United Kingdom, Netherlands, Denmark, and Sweden). 9 , 30 , 31 , 33 , 36 , 37 , 38 , 41 Finally, 1 was undertaken in Australia, comprising 350 patients.…”

Metformin in Esophageal Carcinoma: Exploring Molecular Mechanisms and Therapeutic Insights

“…An accumulating body of evidence strongly suggests that metformin holds promise as a chemopreventive agent. Arai et al conducted a multicenter retrospective cohort analysis to investigate the chemopreventive effects of commonly used drugs on ESCC and EAC [ 45 ]. They showed that the use of PPIs, aspirin, cyclooxygenase-2 inhibitor (COX2I), steroids, statins, and metformin was associated with a lower risk of ESCC compared to non-use.…”

The Complex Interaction between Proton Pump Inhibitors and Cancer Treatment

“…The type of esophageal cancer varies region, with squamous cell carcinoma comprising more than 90% of cases in Asian countries like Japan, South Korea, and China, while adenocarcinoma accounts for 50 to 70% in Europe and the United States, with squamous cell carcinoma representing about 3% to 5%. PPIs do not appear to play a protective or risk-inducing role in esophageal adenocarcinoma [13], but they may have a preventive effect in esophageal squamous-cell carcinoma [14]. Moreover, PPI use has been associated with an increased risk of pancreatic cancer, liver cancer, and biliary tract cancer [15][16][17].…”