Use of benzodiazepines or benzodiazepine related drugs and the risk of cancer: a population-based case-control study

Br J Clin Pharmacol. 2013 May;75(5):1356-64. doi: 10.1111/bcp.12001.


Aim: 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.

Method: 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.

Conclusion: 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.

MeSH terms

  • Aged
  • Benzodiazepines / adverse effects*
  • Case-Control Studies
  • Denmark
  • Female
  • Humans
  • Hypnotics and Sedatives / adverse effects*
  • Male
  • Middle Aged
  • Neoplasms / chemically induced*
  • Odds Ratio
  • Registries
  • Risk Factors
  • Time Factors


  • Hypnotics and Sedatives
  • Benzodiazepines