pattern for total cancer incidence because the
pattern for total cancer incidence because the individuals using 180e360 DDD sedative-hypnotics showed the highest HR for overall cancer. It is possible that the use of extreme levels of sed-atives might result in different health outcomes such as death. Lastly, in this analysis, we used prescription data; this may not exactly reflect the actual amount of drug use.
In conclusion, we found a significantly increased incidence of overall cancer among women who used sedative-hypnotic medi-cations, and several specific cancers showed increased risk among both men and women who used sedative-hypnotics. Men who used sedative-hypnotics had increased incidence of lung, brain, and prostate cancer and decreased incidence of Sotrastaurin (AEB071) and colon cancer. Women who used sedative-hypnotics had increased inci-dence of thyroid, breast, ovarian, liver, and lung cancer. Further large-population studies that include data on potential covariates are needed to confirm the relationship of overall cancer risk and risk for specific types of cancer with use of various sedative-hypnotic medications.
This study was supported by the research fund of the Mental Health Technology Development Project (Project No. HM15C1197).
This manuscript was edited by Ms. Bethanie Rammer, BioMedEdits.com, for clarity, consistency, and English-language usage. Dr. Jung is supported by the Yerby Postdoctoral Fellowship of Harvard School of Public Health.
Conflict of interest
The authors have no conflicts of interest to declare.
The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the following link: https://doi.org/10.1016/j.sleep.2019.03.018.
KCD-6 codes for cancers included in the current study
Code Type of cancer
Cxx Overall cancer C15 Esophageal cancer C16 Gastric cancer C18eC20 Colorectal cancer C22 Liver cancer C33eC34 Lung cancer C50 Breast cancer C53 Utero-cervix cancer C56 Ovarian cancer C61 Prostate cancer C64 Renal cancer C70eC71 Brain cancer C73 Thyroid cancer
 Hardell L, Fredrikson M, Axelson O. Case-control study on colon cancer regarding previous diseases and drug intake. Int J Oncol 1996;8:439e44.  Pottegard A, Friis S, Andersen M, et al. Use of benzodiazepines or benzodi-azepine related drugs and the risk of cancer: a population-based case-control study. Br J Clin Pharmacol 2013;75:1356e64.
 Harnod T, Lin CL, Sung FC, et al. An association between benzodiazepine use and occurrence of benign brain tumors. J Neurol Sci 2014;336:8e12.  Iqbal U, Nguyen PA, Syed-Abdul S, et al. Is long-term use of benzodiazepine a risk for cancer? Medicine (Baltimore) 2015;94:e483.  Kripke DF, Langer RD, Kline LE. Hypnotics' association with mortality or cancer: a matched cohort study. BMJ Open 2012;2:e000850.  Cheol Seong S, Kim YY, Khang YH, et al. Data resource profile: the national health information database of the national health insurance Service in South Korea. Int J Epidemiol 2017;46:799e800.  Methodology WCCfDS. Guidelines for ATC classification and DDD assignment 2013. 2012. Oslo.  Korea S. Korean standard classification of diseases-6. In: Classification KSS; 2010.
 Organization WH. International classification of diseases. 2016. 10th version.
 Friedman GD, Coates AO, Potter JD, et al. Drugs and colon cancer. Pharma-coepidemiol Drug Saf 1998;7:99e106.  Coogan PF, Rosenberg L, Palmer JR, et al. Risk of ovarian cancer according to use of antidepressants, phenothiazines, and benzodiazepines (United States). Cancer Causes Control 2000;11:839e45.
 Kao CH, Sun LM, Su KP, et al. Benzodiazepine use possibly increases cancer risk: a population-based retrospective cohort study in Taiwan. J Clin Psychi-atry 2012;73:e555e60.
 Kim HB, Myung SK, Park YC, et al. Use of benzodiazepine and risk of cancer: a meta-analysis of observational studies. Int J Cancer 2017;140:513e25.  Dublin S, Rossing MA, Heckbert SR, et al. Risk of epithelial ovarian cancer in relation to use of antidepressants, benzodiazepines, and other centrally acting medications. Cancer Causes Control 2002;13:35e45.
 Halapy E, Kreiger N, Cotterchio M, et al. Benzodiazepines and risk for breast cancer. Ann Epidemiol 2006;16:632e6.  Rosenberg L, Palmer JR, Zauber AG, et al. Relation of benzodiazepine use to the risk of selected cancers: breast, large bowel, malignant melanoma, lung,
 Harlow BL, Cramer DW. Self-reported use of antidepressants or benzodiaze-pine tranquilizers and risk of epithelial ovarian cancer: evidence from two combined case-control studies (Massachusetts, United States). Cancer Causes Control 1995;6:130e4.