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Association between sedative-hypnotic medication use and incidence of cancer in Korean Nation Health Insurance Service data
Sun Jae Jung a, b, Joonki Lee c, Jae-Won Choi d, Soohyun Kim e, Aesun Shin c, f, *, Yu Jin Lee e, ** a Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
b Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
c Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
d Department of Neuropsychiatry, Eulji University School of Medicine, Eulji General Hospital, Seoul, Republic of Korea
e Department of Psychiatry and Center for Sleep and Chronobiology, Seoul National University College of Medicine, Seoul, Republic of Korea
f Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
Received in revised form
Objectives: We aimed to investigate the association between the use of various sedative-hypnotics and the incidence of overall and individual cancers in Latrunculin A large, population-based, retrospective cohort study. Methods: We selected a 5% random sample of individuals aged 50 years or older from data maintained by the Korean National Health Insurance Service for the years 2002e2015, excluding individuals with a prior diagnosis of cancer and with any sedative-hypnotic use in the initial two years of follow-up, leaving 236,759 participants for the final analysis. Exposure to sedative-hypnotics was defined by type of drug, standardized to a defined daily dose, and coded as a time-varying variable. Cox proportional hazard models were applied after adjusting for sex, socio-economic status, and comorbidities.
Conclusion: We found a significant increase in overall cancer incidence among participants who used sedative-hypnotics, and both male and female sedative-hypnotic users had significantly increased risk for certain types of cancer.
In chronic insomnia patients, several sedative-hypnotic medi-cations are prescribed for an average of five years . Commonly
* Corresponding author. Department of Psychiatry and Center for Sleep and Chronobiology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea. Fax: þ82 2 744 7241. ** Corresponding author. Department of Preventive Medicine, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 03080, Republic of
prescribed medications include benzodiazepines, zolpidem, low-dose anti-psychotics, and anti-depressants. Benzodiazepines were prescribed to approximately 9% of the elderly population in the United States in 2008 , and 24% in Korea between 2007 and 2011 with increasing rate .
Among the issues related to the side-effects of sedative-hypnotics , the association between the use of sedative-hypnotic medications and various types of cancers has been un-der continuous debate. Initially, breast cancer was assessed in relation to sedative-hypnotic medication use in several studies, but no significant results were found [4,5]. Hardell et al., reported a null association between use of these medications and colon cancer . However, in recent studies, sedative-hypnotic
medication use was associated with increased risk of several cancers, such as liver cancer, prostate cancer, bladder/kidney cancer, esophageal, and stomach cancer, lung cancer, and pancreatic cancer [7e9].
Notably, all of the studies showing an increased risk of specific cancers assessed benzodiazepines only [7e9]. Even the study conducted by Kripke et al. , which evaluated the effect of other sedative-hypnotics rather than benzodiazepines alone, observed no effect for non-benzodiazepine medications or for benzodiazepines on specific cancers. In addition, most previous work has been conducted using a caseecontrol design, which inevitably possesses limitations on distinguishing the temporal sequence between use of sedative-hypnotics and cancer.
Therefore, we aimed to investigate the effects of the use of various sedative-hypnotics on different cancers in a large population-based cohort with long-term follow-up.