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Relationship of Zolpidem and Cancer Risk: A Taiwanese Population-Based Cohort Study

  • Chia-Hung Kao
    Correspondence
    Correspondence: Address to Chia-Hung Kao, MD, Institute of Clinical Medicine Science, College of Medicine, China Medical University; No. 2, Yuh-Der Rd, Taichung 404, Taiwan
    Affiliations
    Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan

    Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan
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  • Li-Min Sun
    Affiliations
    Department of Radiation Oncology, Zuoying Armed Forces General Hospital, Kaohsiung, Taiwan
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  • Ji-An Liang
    Affiliations
    Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan

    Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan
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  • Shih-Ni Chang
    Affiliations
    Institute of Public Health, College of Public Health, China Medical University, Taichung, Taiwan

    Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University, Taichung, Taiwan

    Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan

    Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
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  • Fung-Chang Sung
    Affiliations
    Institute of Public Health, College of Public Health, China Medical University, Taichung, Taiwan

    Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
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  • Chih-Hsin Muo
    Correspondence
    Chih-Hsin Muo, MS, China Medical University Hospital; No. 2 Yuh-Der Road, Taichung 404, Taiwan
    Affiliations
    Institute of Public Health, College of Public Health, China Medical University, Taichung, Taiwan

    Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
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      Abstract

      Objective

      To evaluate the relationship between the use of zolpidem and subsequent cancer risk in Taiwanese patients.

      Methods

      We used data from the National Health Insurance system of Taiwan to investigate whether use of zolpidem was related to cancer risk. For the study cohort, we identified 14,950 patients who had received a first prescription for zolpidem from January 1, 1998, through December 31, 2000. For each zolpidem user, we selected randomly 4 comparison patients without a history of using zolpidem who were frequency-matched by sex, age, and year of the index date. Incidence rates of all cancers and selected site-specific cancers were measured by the end of 2009, and related hazard ratios (HRs) and 95% confidence intervals (CIs) of the cancer were measured as well.

      Results

      The risk of developing any cancer was greater in patients using zolpidem than in nonusers (HR, 1.68; 95% CI, 1.55-1.82). The stratified analysis showed that the overall HR for high-dosage zolpidem (≥300 mg/y) was 2.38. The site-specific cancer risk was the highest for oral cancer (HR, 2.36; 95% CI, 1.57-3.56), followed by kidney cancer, esophageal cancer, breast cancer, liver cancer, lung cancer, and bladder cancer (HR, 1.60; 95% CI, 1.06-2.41). Men were at higher risk than women.

      Conclusion

      This population-based study revealed some unexpected findings, suggesting that the use of zolpidem may be associated with an increased risk of subsequent cancer. Further large-scale and in-depth investigations in this area are warranted.

      Abbreviations and Acronyms:

      CI (confidence interval), CIN (cervical intraepithelial neoplasia), CIS (carcinoma in situ), HR (hazard ratio), ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification), NHI (National Health Insurance), NHIRD (National Health Insurance Research Database), NHRI (National Health Research Institute)
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      Linked Article

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          Most sleep clinicians know the sinking feeling associated with encountering patients who are frantic about their inability to sleep. Such patients have often taken most hypnotics that we have heard of (and some that we haven't) and visited several other practitioners for this problem. They report being fearful that their insomnia is causing problems with daytime functioning and with health. They are often able to quote recent media reports associating “poor sleep” or “sleep disorders” with bad outcomes, including death.
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        Mayo Clinic ProceedingsVol. 87Issue 10
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          We appreciate Dr Geller's comments. He provides more possible explanations for our findings1 on the basis of some potential pharmacologic and pathophysiologic mechanisms.
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          The valuable cohort contribution by Kao et al1 associating narcotic zolpidem consumption with heightened iatrogenic malignancy risks would be considerably more compelling if accompanied by proposition of a distinct plausible pathophysiologic mechanism. The most favorably received mechanism would define associations between the physiologic effects of zolpidem that are common to other pharmacologic agents and diagnoses that effect similar intermediary stepwise events epidemiologically linked to oncogenesis.
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