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

• Published in: The American journal of gastroenterology Vol. 115; no. 1; pp. 73 - 78
• Main Authors: Wang, Qiao-Li, Santoni, Giola, Ness-Jensen, Eivind, Lagergren, Jesper, Xie, Shao-Hua
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer 01.01.2020; Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins
• Subjects: Age; Alcohol; Antidiabetics; Calendars; Codes; Cohort analysis; Drug dosages; Esophageal cancer; Esophageal Neoplasms - diagnosis; Esophageal Neoplasms - epidemiology; Esophageal Neoplasms - prevention & control; Esophageal Squamous Cell Carcinoma - diagnosis; Esophageal Squamous Cell Carcinoma - epidemiology; Esophageal Squamous Cell Carcinoma - prevention & control; Female; Follow-Up Studies; Gastroenterology; Humans; Hypoglycemic Agents - pharmacology; Incidence; Male; Medical prognosis; Metformin - pharmacology; Middle Aged; Nonsteroidal anti-inflammatory drugs; Patient Compliance; Population; Population Surveillance; Population-based studies; Prognosis; Prospective Studies; Registries; Risk Assessment - methods; Risk Factors; Skin cancer; Smoking; Squamous cell carcinoma; Sweden - epidemiology; Tobacco; Sweden
• ISSN: 0002-9270; 1572-0241; 1572-0241
• DOI: 10.14309/ajg.0000000000000478

Esophageal cancer is a highly fatal malignant neoplasm, with 2 etiologically different histological types. A large prospective study is expected to elucidate the specific risk of the 90% subtype of esophageal cancer, esophageal squamous cell carcinoma (ESCC), with metformin therapy. This study aims to determine the association between metformin use and incident ESCC risk. This was a nationwide population-based prospective cohort study conducted in Sweden in 2005-2015. Among 8.4 million participants identified in the cohort, 411,603 (5%) were metformin users. The users were compared with 10 times as many frequency-matched nonusers of metformin (n = 4,116,030) by age and sex. Metformin use was treated as a time-varying variate, and multivariable cause-specific proportional hazards model was used to calculate hazard ratios (HR) with 95% confidence intervals (CI) for ESCC, adjusted for age, sex, calendar year, residence area, tobacco smoking, alcohol overconsumption, and use of nonsteroidal anti-inflammatory drugs or statins. The incidence rates of ESCC were 3.5 per 100,000 person-years among the metformin users and 5.3 per 100,000 person-years in the nonusers. Metformin users overall were at a decreased risk of ESCC compared with nonusers (HR 0.68, 95% CI 0.54-0.85). The decrease in risk was more pronounced in new metformin users (HR 0.44, 95% CI 0.28-0.64) and participants aged 60-69 years (HR 0.45, 95% CI 0.31-0.66). Metformin use decreases the risk of developing ESCC.