title: Digoxin use and the risk for colorectal cancer.
abstract: OBJECTIVE
  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 record database representative of the broader UK population. Study cases were defined as those with a diagnostic code for CRC. Each case was matched to up to four 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 with 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.
authors.affiliation: Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA, USA; Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA; Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; The Integrated Cancer Prevention Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ben
authors.initials: B
authors.lastname: Boursi
authors.forename: Kevin
authors.initials: K
authors.lastname: Haynes
authors.forename: Ronac
authors.initials: R
authors.lastname: Mamtani
authors.forename: Yu-Xiao
authors.initials: YX
authors.lastname: Yang
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000437:Alcoholism / Q000453:epidemiology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D015992:Body Mass Index; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D015897:Comorbidity; D004077:Digoxin / Q000009:adverse effects*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000453:epidemiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004077:Digoxin
keywords: cancer; colorectal; digoxin; pharmacoepidemiology; risk factor