title: Is long-term use of benzodiazepine a risk for cancer?
abstract: The carcinogenicity of benzodiazepines (BZDs) is still unclear. We aimed to assess whether long-term benzodiazepines use is risk for cancer.We conducted a longitudinal population-based case-control study by using 12 years from Taiwan National Health Insurance database and investigated the association between BZDs use and cancer risk of people aged over 20 years. During the study period, 42,500 cases diagnosed with cancer were identified and analyzed for BZDs use. For each case, six eligible controls matched for age, sex, and the index date (ie, free of any cancer in the date of case diagnosis) by using propensity score. For appropriate risk estimation, we observed the outcomes according to their length of exposure (LOE) and defined daily dose (DDD). To mimic bias, we adjusted with potential confounding factors such as medications and comorbid diseases which could influence for cancer risk during the study period. The data was analyzed by using Cox proportional hazard regression and conditional logistic regression.The finding unveils benzodiazepines use into safe and unsafe groups for their carcinogenicity. The use of diazepam (HR, 0.96; 95%CI, 0.92-1.00), chlorodizepoxide (HR, 0.98; 95%CI, 0.92-1.04), medazepam (HR, 1.01; 95%CI, 0.84-1.21), nitrazepam (HR, 1.06; 95%CI, 0.98-1.14), oxazepam (HR, 1.05; 95%CI, 0.94-1.17) found safer among BZDs. However, clonazepam (HR, 1.15; 95%CI, 1.09-1.22) were associated with a higher risk for cancers. Moreover, specific cancer risk among BZDs use was observed significantly increased 98% for brain, 25% for colorectal, and 10% for lung, as compared with non-BZDs use.Diazepam, chlordiazepoxide, medazepam, nitrazepam, and oxazepam are safe among BZDs use for cancer risk. Our findings could help physicians to select safer BZDs and provide an evidence on the carcinogenic effect of benzodiazepines use by considering the LOE and DDD for further research.
authors: From the Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan (UI, P-AN, SS-A, H-CY, CWH, M-HH, YY, YC(J)L); Institute of Biomedical Informatics, National Yang Ming University, Taipei, Taiwan (H-CY); School of Health Care Administration, Taipei Medical University, Taipei, Taiwan (W-SJ); Department of Health, Taipei Hospital, Taiwan (M-HH); City of Hope, Duarte, CA, USA (YY); Department of Dermatology, Wan Fang Hospital, Taipei, Taiwan (Y-C(J)L).
authors: Usman
authors: U
authors: Iqbal
authors: Phung-Anh
authors: PA
authors: Nguyen
authors: Shabbir
authors: S
authors: Syed-Abdul
authors: Hsuan-Chia
authors: HC
authors: Yang
authors: Chih-Wei
authors: CW
authors: Huang
authors: Wen-Shan
authors: WS
authors: Jian
authors: Min-Huei
authors: MH
authors: Hsu
authors: Yun
authors: Y
authors: Yen
authors: Yu-Chuan Jack
authors: YJ
authors: Li
mesh_terms: D001569:Benzodiazepines / Q000008:administration & dosage / Q000009:adverse effects*; D002273:Carcinogens; D016022:Case-Control Studies; D002707:Chlordiazepoxide / Q000009:adverse effects; D002998:Clonazepam / Q000009:adverse effects; D003975:Diazepam / Q000009:adverse effects; D005260:Female; D006801:Humans; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008472:Medazepam / Q000009:adverse effects; D008875:Middle Aged; D009567:Nitrazepam / Q000009:adverse effects; D010076:Oxazepam / Q000009:adverse effects; D016016:Proportional Hazards Models
chemical_list: D002273:Carcinogens; D001569:Benzodiazepines; D002998:Clonazepam; D010076:Oxazepam; D002707:Chlordiazepoxide; D009567:Nitrazepam; D008472:Medazepam; D003975:Diazepam