Use of benzodiazepine and risk of cancer: A meta‐analysis of observational studies

• Published in: International journal of cancer Vol. 140; no. 3; pp. 513 - 525
• Main Authors: Kim, Hong‐Bae, Myung, Seung‐Kwon, Park, Yon Chul, Park, Byoungjin
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.02.2017
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; benzodiazepine; Benzodiazepines - adverse effects; Cancer; Case-Control Studies; Cohort Studies; Female; Humans; Male; Medical research; meta‐analysis; Neoplasms - chemically induced; Observational Studies as Topic; observational study; Psychotropic drugs; Research Design; Risk; Risk Assessment; Risk factors; Young Adult; meta-analysis; cancer; benzodiazepine; observational study
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.30443

Several observational epidemiological studies have reported inconsistent results on the association between the use of benzodiazepine and the risk of cancer. We investigated the association by using a meta‐analysis. We searched PubMed, EMBASE, and the bibliographies of relevant articles to locate additional publications in January 2016. Three evaluators independently reviewed and selected eligible studies based on predetermined selection criteria. Of 796 articles meeting our initial criteria, a total of 22 observational epidemiological studies with 18 case‐control studies and 4 cohort studies were included in the final analysis. Benzodiazepine use was significantly associated with an increased risk of cancer (odds ratio [OR] or relative risk [RR] 1.19; 95% confidence interval 1.16–1.21) in a random‐effects meta‐analysis of all studies. Subgroup meta‐analyses by various factors such as study design, type of case‐control study, study region, and methodological quality of study showed consistent findings. Also, a significant dose‐response relationship was observed between the use of benzodiazepine and the risk of cancer (p for trend <0.01). The current meta‐analysis of observational epidemiological studies suggests that benzodiazepine use is associated with an increased risk of cancer. What's new? In recent years, the question of whether sedative‐hypnotic benzodiazepine drugs increase cancer risk has emerged. Evidence for a direct association from animal studies is inconclusive, however, and cohort studies suggest that while some benzodiazepines are associated with increased cancer risk, others are not. The present meta‐analysis of observational studies published between 1982 and 2014 shows that the use of various benzodiazepines, including alprazolam, clonazepam, diazepam, oxazepam, and temazepam, was consistently associated with an increased risk of cancer, overall and in subgroup analyses. The association was characterized by a dose‐response relationship, with risk elevated for multiple cancer types.