title: Use of benzodiazepines or benzodiazepine related drugs and the risk of cancer: a population-based case-control study.
abstract: OBJECTIVE
  Studies of the carcinogenic potential of benzodiazepines and related drugs (BZRD) have been equivocal. A recent study reported a 35% excess cancer risk among users of hypnotics, including benzodiazepines.
  
  
  METHODS
  Using Danish nationwide registers, we conducted a matched case-control study of the association between BZRD and cancer risk. During 1 January 2002 and 31 December 2009, we identified 152 510 cases with a first time cancer who were matched (1:8) by age and gender to 1,220,317 cancer-free controls. A new-user design was applied by excluding all subjects who had used anxiolytics, hypnotics or sedatives during the first 2 years of available prescription data (1995-6). Odds ratios (ORs) with 95% confidence intervals (CI) were estimated using conditional logistic regression, adjusting for potential confounders. In the primary analysis, long term use of BZRD was defined by a cumulative amount of ≥500 defined daily doses of BZRD within a period of 1 to 5 years prior to the index date.
  
  
  RESULTS
  The adjusted OR for cancer associated with BZRD use was 1.09 (95% CI 1.04, 1.14). ORs were close to unity for most cancer sites, except stomach 1.40 (95% CI 1.05, 1.88), oesophagus 1.43 (95% CI 1.01, 2.02), liver 1.81 (95% CI 1.18, 2.80), lung 1.38 (95% CI 1.23, 1.54), pancreas 1.35 (95% CI 1.02, 1.79) and kidney 1.39 (95% CI 1.01, 1.91). For tobacco-related cancers, the OR was 1.15 (95% CI 1.09, 1.22) and for the remaining cancer sites 1.01 (95% CI 0.94, 1.08). Sub-group analyses revealed only small differences between different levels of exposure or different patient subgroups.
  
  
  CONCLUSIONS
  BZRD use was not associated with an overall increase in cancer risk, except for what is likely explained by minor lifestyle confounding, e.g. smoking.
authors.affiliation: Clinical Pharmacology, Institute of Public Health, University of Southern Denmark, DK-5000, Odense C, Denmark. apottegaard@health.sdu.dk
authors.forename: Anton
authors.initials: A
authors.lastname: Pottegård
authors.forename: Søren
authors.initials: S
authors.lastname: Friis
authors.forename: Morten
authors.initials: M
authors.lastname: Andersen
authors.forename: Jesper
authors.initials: J
authors.lastname: Hallas
mesh_terms: D000368:Aged; D001569:Benzodiazepines / Q000009:adverse effects*; D016022:Case-Control Studies; D003718:Denmark; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000139:chemically induced*; D016017:Odds Ratio; D012042:Registries; D012307:Risk Factors; D013997:Time Factors
chemical_list: D006993:Hypnotics and Sedatives; D001569:Benzodiazepines