Psychiatry Investig.  2018 Sep;15(9):900-906. 10.30773/pi.2018.05.02.1.

Benzodiazepine-Associated Carcinogenesis: Focus on Lorazepam-Associated Cancer Biomarker Changes in Overweight Individuals

• Ku SC
• Ho PS
• Tseng YT
• Yeh TC
• Cheng SL
• Liang CS

• KMID: 2424023
• DOI: http://doi.org/10.30773/pi.2018.05.02.1

Abstract

OBJECTIVE
Cellular, animal, and human epidemiological studies suggested that benzodiazepines increase the risk of cancer and cancer mortality. Obesity is also clearly linked to carcinogenesis. However, no human studies have examined benzodiazepine-associated carcinogenesis as assessed by changes in cancer biomarkers.
METHODS
A total of 19 patients were recruited, and received a 6-week treatment of 0.5 mg lorazepam. The measured cancer biomarkers were angiopoietin-2 (ANG-2), soluble CD40 ligand, epidermal growth factor, endoglin, soluble Fas ligand (sFASL), heparin-binding EGF-like growth factor (HB-EGF), insulin-like growth factor binding protein, interleukin (IL)-6, IL-8, IL-18, plasminogen activator inhibitor (PLGF), placental growth factor, transforming growth factor (TGF)-α, tumor necrosis factor (TNF)-α, urokinase-type plasminogen (uPA), vascular endothelial growth factor (VEGF)-A, VEGF-C, and VEGF-D.
RESULTS
Six cancer biomarkers were significantly increased in all patients as a whole. The subgroup analysis revealed a distinct pattern of change. Overweight patients showed a significant increase in 11 cancer biomarkers, including ANG-2, sFASL, HB-EGF, IL-8, PLGF, TGF-α, TNF-α, uPA, VEGF-A, VEGF-C, and VEGF-D. However, normal-weight patients did not show any changes in cancer biomarkers.
CONCLUSION
Adiposity may have primed the carcinogenic potential, leading to lorazepam-associated carcinogenesis in overweight patients. Epidemiological studies addressing this issue should consider the potential modulator contributing to benzodiazepine-associated carcinogenesis.

Keyword

Benzodiazepines; Cancer; Carcinogenesis; Lorazepam; Overweight

MeSH Terms

Adiposity
Angiopoietin-2
Animals
Benzodiazepines
Biomarkers, Tumor
Carcinogenesis*
Carrier Proteins
CD40 Ligand
Epidemiologic Studies
Epidermal Growth Factor
Fas Ligand Protein
Heparin-binding EGF-like Growth Factor
Humans
Interleukin-18
Interleukin-8
Interleukins
Lorazepam
Mortality
Obesity
Overweight*
Plasminogen
Plasminogen Activators
Transforming Growth Factors
Tumor Necrosis Factor-alpha
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor C
Vascular Endothelial Growth Factor D
Angiopoietin-2
Benzodiazepines
Biomarkers, Tumor
CD40 Ligand
Carrier Proteins
Epidermal Growth Factor
Fas Ligand Protein
Heparin-binding EGF-like Growth Factor
Interleukin-18
Interleukin-8
Interleukins
Lorazepam
Plasminogen
Plasminogen Activators
Transforming Growth Factors
Tumor Necrosis Factor-alpha
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor C
Vascular Endothelial Growth Factor D