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

Abstract

ObjectiveCellular, 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. MethodsA 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. ResultsSix 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. ConclusionAdiposity 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.

The Role of Metabolic Syndrome in Endometrial Cancer: A Review

“…The level of TNF-α in circulating blood of obese patients is increased, and the increased level of TNF-α is closely related to the poor prognosis of endometrial cancer patients (76). In addition, studies have reported that 11 cancer markers in overweight patients are significantly higher than those in normal weight patients, including ANG-2, sFASL, HB-EGF, IL-8, PLGF, TGF-α, TNF-α, uPA, VEGF-A, VEGF-C, and VEGF-D (77). Compared with lean mice, C57BL/6 mice induced by a high-fat diet had higher levels of serum free fatty acids and TNF-α and higher accumulation of macrophages in adipose tissue (78).…”

Association of Benzodiazepine Receptor Agonist Use With Changes in Psoriasis Severity in Adult Population: A Population-Based Study

“…Recently, some studies reported that angiogenic factors may play an important role in the pathogenesis of psoriasis, and accumulating evidence indicates that the levels of vascular endothelial growth factor (VEGF) may be abnormal among the psoriasis population ( Canavese et al, 2010 ; Flisiak et al, 2010 ; Henno et al, 2010 ; Wang et al, 2016 ; Sankar et al, 2017 ). In addition, one recent study observed that the levels of biomarkers, including IL-8, TGF-α and VEGF-A, were significantly elevated after 6 weeks of treatment with the BZRA lorazepam ( Ku et al, 2018 ). Among overweight patients, the serum levels of IL-8, TGF-α, TNF-α, VEGF-A, VEGF-C and VEGF-D were significantly increased after lorazepam treatment ( Ku et al, 2018 ).…”

“…In addition, one recent study observed that the levels of biomarkers, including IL-8, TGF-α and VEGF-A, were significantly elevated after 6 weeks of treatment with the BZRA lorazepam ( Ku et al, 2018 ). Among overweight patients, the serum levels of IL-8, TGF-α, TNF-α, VEGF-A, VEGF-C and VEGF-D were significantly increased after lorazepam treatment ( Ku et al, 2018 ). Accordingly, BZRAs may elevate the levels of some factors, such as IL-8, TNF-α VEGF, associated with the development of psoriasis ( Arican et al, 2005 ; Flisiak et al, 2010 ; Ku et al, 2018 ).…”

“…Among overweight patients, the serum levels of IL-8, TGF-α, TNF-α, VEGF-A, VEGF-C and VEGF-D were significantly increased after lorazepam treatment ( Ku et al, 2018 ). Accordingly, BZRAs may elevate the levels of some factors, such as IL-8, TNF-α VEGF, associated with the development of psoriasis ( Arican et al, 2005 ; Flisiak et al, 2010 ; Ku et al, 2018 ). Therefore, it was plausible that BZRA may be an aggravating factor for psoriasis.…”

“…Only one recent study found that BZRAs may be a risk factor for new-onset psoriasis ( Li et al, 2019 ). To date, it is uncertain whether BZRAs are aggravating factors even though BZRAs can elevate some biomarkers associated with the development of psoriasis ( Arican et al, 2005 ; Flisiak et al, 2010 ; Ku et al, 2018 ). No clear clinical evidence is available to guide physicians in the use of these drugs for patients with psoriasis.…”