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Keywords:

  • benzodiazepines;
  • cancer;
  • case–control study;
  • pharmacoepidemiology;
  • population based

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.