Purpose
Cardiac glycosides affect several pathways central for tumor formation. We sought to evaluate the association between digoxin use and colorectal cancer (CRC) risk.
Methods
We conducted a nested case-control study using The Health Improvement Network (THIN), a medical records database representative of the broader United Kingdom population. Study cases were defined as those with a diagnostic code for CRC. Each case was matched to up to 4 eligible controls on age, sex, practice site, and duration of follow-up before index date using incidence density sampling. Exposure of interest was digoxin therapy before index date. The odds ratios (ORs) and 95% confidence intervals (CIs) for CRC associated with digoxin use were estimated using conditional logistic regression analysis, adjusted for BMI, alcoholism, smoking history, diabetes mellitus, heart disease, chronic NSAIDs use and previous screening colonoscopies.
Results
The case control analysis included 20,990 CRC patients and 82,054 controls whose mean follow up time before index date was 6.5 years (SD 4.0). The adjusted OR for CRC among current digoxin users was increased compared to non-users with an adjusted ORs of 1.41 (95%CI 1.25–1.59, p<0.0001) 1.45 (95%CI 1.22–1.72, p<0.0001) and 1.41 (95%CI 1.00–1.99, p=0.049) for first prescriptions 1–5 years, 5–10 years and more than 10 years before index date respectively. Similar results were observed when cumulative duration and number of digoxin prescriptions were analyzed. The risk was not elevated for past digoxin users.
Conclusions
Current digoxin use is associated with increased CRC risk.