Oncotarget

Research Papers:

Digitalis use and risk of gastrointestinal cancers: A nationwide population-based cohort study

Shao-Hua Xie _, Tomas Jernberg, Fredrik Mattsson and Jesper Lagergren

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Oncotarget. 2017; 8:34727-34735. https://doi.org/10.18632/oncotarget.16151

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Abstract

Shao-Hua Xie1, Tomas Jernberg2,3, Fredrik Mattsson1 and Jesper Lagergren1,4

1Upper Gastrointestinal Surgery, Department of Molecular medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

3Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden

4Division of Cancer Studies, King’s College London, London, United Kingdom

Correspondence to:

Shao-Hua Xie, email: shaohua.xie@ki.se

Keywords: digitalis, digoxin, gastrointestinal cancers, medication, chemoprevention

Received: December 22, 2016     Accepted: February 08, 2017     Published: March 13, 2017

ABSTRACT

Background: Gastrointestinal cancers are characterized by a male predominance, suggesting a role of sex hormones. We hypothesized that digitalis medication, due to its estrogenic properties, decreases the risk of male-predominated gastrointestinal cancers.

Results: Long -term digitalis use (≥2 years) was followed by decreased risk for several gastrointestinal cancers, but associations were statistically significant only for liver cancer (hazard ratio [HR]=0.40, 95% confidence interval (CI) 0.16-0.98). Short-term (<1 year) use was associated with an increased risk of esophageal squamous cell carcinoma (HR=1.79, 95% CI 1.01-3.17), colorectal cancer (HR=1.72, 95% CI 1.57-1.89), gallbladder cancer (HR=1.93, 95% CI 1.04-3.59), and pancreatic cancer (HR=1.33, 95% CI 1.00-1.76), but no such increase was found among long-term users.

Methods: We performed a nationwide population-based cohort study in Sweden. Participants included 156,385 individuals using digitalis and a reference group of 551,933 users of organic nitrates between 2005 and 2013, who were identified in the Swedish Prescribed Drug Register. New diagnoses of gastrointestinal cancers were identified from the Swedish Cancer Register. Hazard ratios of gastrointestinal cancers in digitalis users compared to users of organic nitrates were calculated from Cox proportional hazards regression with adjustment for sex, age, municipality of residence and comorbidity.

Conclusions: This study suggests a decreased risk of male-predominated gastrointestinal cancers, particularly of liver cancer, in long-term users of digitalis. Short-term use may be associated with an increased risk of esophageal squamous cell carcinoma, colorectal cancer, gallbladder cancer, and pancreatic cancer.The use of digitalis as preventive or therapeutic agents remains to be fully evaluated.


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