Is Long-term Use of Benzodiazepine a Risk for Cancer?

Iqbal, Usman; Nguyen, Phung‐Anh; Syed-Abdul, Shabbir; Yang, Hsuan-Chia; Huang, Chih-Wei; Jian, Wen-Shan; Hsu, Min-Huei; Yen, Yun; Li, Yu-Chuan

doi:10.1097/md.0000000000000483

Cited by 52 publications

(37 citation statements)

References 34 publications

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“…In attempts to get a clear answer to this quandary, Kim et al published a 2016 meta-analysis of 22 observational studies (18 case–control and 4 cohort) which concluded an overall estimate of 19% increased cancer risk, with a significant dose-response trend, among benzodiazepine users over non-users [ 140 ]. There does exist a fine degree of granularity when it comes to the determination of cancer risk from benzodiazepines/Z-drugs as certain types of cancer (i.e., esophageal, brain, pancreatic) and certain agents (lorazepam, clonazepam, zopiclone) carry greater statistical weight, driving the overall association [ 137 , 140 ]. Given that most of the studies included in the meta-analysis are retrospective, the authors address the limitations fairly by reminding us of confounding by indication (cancer patients more likely to use anxiolytic medication) and unmeasured confounding (alcohol and smoking) [ 140 ].…”

Section: Cancermentioning

confidence: 99%

Benzodiazepines and Z-Drugs: An Updated Review of Major Adverse Outcomes Reported on in Epidemiologic Research

2017

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Various adverse events resulting from, or associated with, benzodiazepine and/or Z-drug use have been extensively reported on and discussed in great detail within the biomedical literature. It is widely accepted that motor vehicle accidents and falls leading to fractures in older adults are major adverse events that have been shown to occur more frequently in users of sedative-hypnotic medication, especially of the benzodiazepine and related Z-drug variety. However, the last few years have seen increasing reports in the literature raising the issue of benzodiazepine and Z-drug exposure in the development of other serious medical issues including dementia, infections, respiratory disease exacerbation, pancreatitis, and cancer. This article provides an overview and interpretation on the current state of evidence regarding each of these associations and proposes what gaps in the evidence for drug-exposure–harm associations need to be addressed in the future for the purpose of evaluating causality of harm as it relates to these drugs.

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Section: Cancermentioning

confidence: 99%

Benzodiazepines and Z-Drugs: An Updated Review of Major Adverse Outcomes Reported on in Epidemiologic Research

2017

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“…The National Health Insurance is a single-payer system that was created by integrating 13 public insurance systems in 1995 to serve all residents of Taiwan. Approximately 99% of the estimated population of 23.7 million residents of Taiwan has been covered by this health-care insurance program since 1999 (12). The Taiwan Department of Health has authorized the National Health Research Institute (NHRI) to manage the claims data of the National Health Insurance Research Database (NHIRD).…”

Section: Methodsmentioning

confidence: 99%

Ankylosing spondylitis and the risk of cancer

Chang

Nguyễn

et al. 2017

Oncology Letters

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Abstract.Cancer is a multifactorial disease, and imbalances of the immune response and sex-associated features are considered risk factors for certain types of cancer. The present study aimed to assess whether ankylosing spondylitis (AS), an immune disorder that predominantly affects young adult men, is associated with an increased risk of cancer. Using the Taiwan National Health Insurance Research Database, a cohort of patients diagnosed with AS between 2000 and 2008 who had no history of cancer prior to enrollment was established (n=5,452). Age-and sex-matched patients without AS served as controls (n=21,808). The results revealed that the overall incidence of cancer was elevated in patients with AS [standardized incidence ratio (SIR), 1.15; 95% confidence interval (CI), 1.03-1.27]. AS carried an increased risk of hematological malignancy in both sexes, colon cancer in females and bone and prostate cancer in males. Young patients with AS (≤35 years) and patients with a Charlson comorbidity index (CCI) ≥2 experienced a higher incidence of cancer (males, SIR 1.92, and 95% CI 1.04-3.26; females, SIR 2.00 and 95% CI 1.46-5.50). The cancer risk was increased during the first 3 years following the diagnosis of AS (SIR 1.49, 95% CI 1.29-1.71), and overall cancer-free survival was significantly decreased in patients with AS patients of both sexes (P<0.0001). Therefore, AS was found to be associated with an increased risk of cancer. All AS patients must be screened for hematological malignancies, for prostate and bone cancer in males, and for colon cancer in females, particularly younger patients with a CCI ≥2.

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“…Among these, 21 articles were excluded because of the following reasons: not relevant to our analysis (n 5 7), insufficient data (n 5 3), using psychotropic medication other than benzodiazepine (n 5 6), data from pre-existing cancer (n 5 3), using cancer mortality as a result, and using an acute biomarker as exposure. The remaining 21 studies including eighteen casecontrol studies 6,7,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] and four cohort studies 8,9,28,29 were included in the final analysis (the study by Kaufman et al 13 was considered as two separate case-control studies). All of the included articles were written in English.…”

Section: Identification Of Relevant Studiesmentioning

confidence: 99%

“…Eight studies 6,7,13,23,[26][27][28] investigated breast cancer, three studies involved ovarian cancer, 14,19,21 two studies looked into colon cancer, 16,18 and five studies involved all types of cancer. 8,[26][27][28][29] They were conducted in the following countries: US (n 5 12), 6,7,[13][14][15]18,19,[21][22][23][24][25] Canada (n 5 2), 13,23 Sweden (n 5 3), 16,17,20 Denmark (n 5 1), 26 France (n 5 1), 29 and Taiwan (n 5 3). 9,27,28 Among 18 case-control studies, 13 studies 7,13,14,17,18,[20][21][22][23][24][25][26][27] were population-based studies, and five studies …”

Section: Characteristics Of Studies Included In the Final Analysismentioning

confidence: 99%

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

et al. 2016

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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.

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Is Long-term Use of Benzodiazepine a Risk for Cancer?

Abstract: Supplemental Digital Content is available in the text

Cited by 52 publications

References 34 publications

Benzodiazepines and Z-Drugs: An Updated Review of Major Adverse Outcomes Reported on in Epidemiologic Research

Benzodiazepines and Z-Drugs: An Updated Review of Major Adverse Outcomes Reported on in Epidemiologic Research

Ankylosing spondylitis and the risk of cancer

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

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