Benzodiazepines use and breast cancer risk: A population-based study and gene expression profiling evidence

Usman Iqbal; Tzu-Hao Chang; Phung-Anh Nguyen; Shabbir Syed-Abdul; Hsuan-Chia Yang; Chih-Wei Huang; Suleman Atique; Wei-Chung Yang; Max Moldovan; Wen-Shan Jian; Min-Huei Hsu; Yun Yen; Yu-Chuan Jack Li

doi:10.1016/j.jbi.2017.08.008

Benzodiazepines use and breast cancer risk: A population-based study and gene expression profiling evidence

J Biomed Inform. 2017 Oct:74:85-91. doi: 10.1016/j.jbi.2017.08.008. Epub 2017 Aug 26.

Authors

Affiliations

¹ Global Health & Development Department, College of Public Health, Taipei Medical University, Taipei, Taiwan; International Center for Health Information Technology (ICHIT), Taipei Medical University, Taipei, Taiwan; Health Informatics Department, COMSATS Institute of Information Technology (CIIT), Islamabad, Pakistan.
² International Center for Health Information Technology (ICHIT), Taipei Medical University, Taipei, Taiwan; Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taiwan.
³ International Center for Health Information Technology (ICHIT), Taipei Medical University, Taipei, Taiwan; Case Western Reserve University School of Medicine, Cleveland, OH, USA.
⁴ International Center for Health Information Technology (ICHIT), Taipei Medical University, Taipei, Taiwan.
⁵ Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taiwan.
⁶ Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taiwan.
⁷ South Australian Health and Medical Research Institute/EMBL Australia, Adelaide, Australia.
⁸ International Center for Health Information Technology (ICHIT), Taipei Medical University, Taipei, Taiwan; School of Health Care Administration, College of Management, Taipei Medical University, Taipei, Taiwan; Faculty of Health Sciences, Macau University of Science and Technology, Macau.
⁹ International Center for Health Information Technology (ICHIT), Taipei Medical University, Taipei, Taiwan; Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taiwan; Office of International Cooperation, Ministry of Health and Welfare, Taiwan.
¹⁰ Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taiwan; City of Hope, Duarte, CA, USA.
¹¹ International Center for Health Information Technology (ICHIT), Taipei Medical University, Taipei, Taiwan; Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taiwan; Department of Dermatology, Wan-Fang Hospital, Taipei, Taiwan. Electronic address: [email protected].

PMID: 28851658
DOI: 10.1016/j.jbi.2017.08.008

Abstract

The aim of this study was to investigate whether long-term use of Benzodiazepines (BZDs) is associated with breast cancer risk through the combination of population-based observational and gene expression profiling evidence. We conducted a population-based case-control study by using 1998 to 2009year Taiwan National Health Insurance Research Database and investigated the association between BZDs use and breast cancer risk. We selected subjects age of >20years old and six eligible controls matched for age, sex and the index date (i.e., free of any cancer at the case diagnosis date) by using propensity scores. A bioinformatics analysis approach was also performed for the identification of oncogenesis effects of BZDs on breast cancer. We used breast cancer gene expression data from the Cancer Genome Atlas and perturbagen signatures of BZDs from the Library of Integrated Cellular Signatures database in order to identify the oncogenesis effects of BZDs on breast cancer. We found evidence of increased breast cancer risk for diazepam (OR, 1.16; 95%CI, 0.95-1.42; connectivity score [CS], 0.3016), zolpidem (OR, 1.11; 95%CI, 0.95-1.30; CS, 0.2738), but not for lorazepam (OR, 1.04; 95%CI, 0.89-1.23; CS, -0.2952) consistently in both methods. The finding for alparazolam was contradictory from the two methods. Diazepam and zolpidem trends showed association, although not statistically significant, with breast cancer risk in both epidemiological and bioinformatics analyses outcomes. The methodological value of our study is in introducing the way of combining epidemiological and bioinformatics approaches in order to answer a common scientific question. Combining the two approaches would be a substantial step towards uncovering, validation and further application of previously unknown scientific knowledge to the emerging field of precision medicine informatics.

Keywords: Benzodiazepines; Bioinformatics; Breast cancer; Gene profiling data; Observational health data; Pharmacoepidemiology; Precision medicine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Benzodiazepines / adverse effects*
Breast Neoplasms / chemically induced*
Breast Neoplasms / genetics*
Case-Control Studies
Female
Gene Expression Profiling*
Humans
Middle Aged
Population Surveillance*
Risk Factors

Substances

Benzodiazepines