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Am J Gastroenterol. 2020 Jan;115(1):73-78. doi: 10.14309/ajg.0000000000000478.

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

Author information

1
Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
2
HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway.
3
Medical Department, Levanger Hospital, Nord-Tr√łndelag Hospital Trust, Levanger, Norway.
4
School of Cancer and Pharmaceutical Sciences, King's College London, London, United Kingdom.

Abstract

OBJECTIVES:

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.

METHODS:

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.

RESULTS:

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).

DISCUSSION:

Metformin use decreases the risk of developing ESCC.

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