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长期使用苯二氮䓬类药物会增加患癌风险吗?

Is long-term use of benzodiazepine a risk for cancer?

作者信息

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 Jack

机构信息

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).

出版信息

Medicine (Baltimore). 2015 Feb;94(6):e483. doi: 10.1097/MD.0000000000000483.

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.

摘要

苯二氮䓬类药物(BZDs)的致癌性仍不明确。我们旨在评估长期使用苯二氮䓬类药物是否会增加患癌风险。我们利用台湾国民健康保险数据库12年的数据进行了一项基于人群的纵向病例对照研究,调查了20岁以上人群使用BZDs与患癌风险之间的关联。在研究期间,共识别出42500例癌症确诊病例,并对其BZDs使用情况进行分析。对于每例病例,通过倾向得分匹配6名年龄、性别和索引日期(即病例诊断日期时无任何癌症)相匹配的合格对照。为了进行适当的风险评估,我们根据暴露时长(LOE)和限定日剂量(DDD)观察结果。为模拟偏差,我们对可能影响研究期间癌症风险的潜在混杂因素进行了调整,如药物和合并症。数据采用Cox比例风险回归和条件逻辑回归进行分析。研究结果根据其致癌性将BZDs的使用分为安全组和不安全组。地西泮(风险比[HR],0.96;95%置信区间[CI],0.92 - 1.00)、氯氮䓬(HR,0.98;95%CI,0.92 - 1.04)、美达西泮(HR,1.01;95%CI,0.84 - 1.21)、硝西泮(HR,1.06;95%CI,0.98 - 1.14)、奥沙西泮(HR,1.05;95%CI,0.94 - 1.17)在BZDs中被发现相对安全。然而,氯硝西泮(HR,1.15;95%CI,1.09 - 1.22)与较高的癌症风险相关。此外,与未使用BZDs相比,使用BZDs人群中特定癌症风险显著增加,脑癌增加98%,结直肠癌增加25%,肺癌增加10%。地西泮、氯氮䓬、美达西泮、硝西泮和奥沙西泮在使用BZDs时对癌症风险是安全的。我们的研究结果可以帮助医生选择更安全的BZDs,并通过考虑LOE和DDD为进一步研究提供关于使用苯二氮䓬类药物致癌作用的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/194d/4602739/3cadba659009/medi-94-e483-g002.jpg

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