Environmental cadmium exposure and pancreatic cancer: Evidence from case control, animal and in vitro studies. (July 2019)

• Record Type: Journal Article
• Authors: Djordjevic, Vladimir R.; Wallace, David R.; Schweitzer, Amie; Boricic, Novica; Knezevic, Djordje; Matic, Slavko; Grubor, Nikola; Kerkez, Mirko; Radenkovic, Dejan; Bulat, Zorica; Antonijevic, Biljana; Matovic, Vesna; Buha, Aleksandra
• Is Part Of: Environment international. Volume 128(2019)
• Page Start: 353
• Page End: 361
• Publication Date: 2019-07
• Subjects: PC pancreatic cancer -- Cd cadmium -- DCFH dichlorofluorescein -- OR odds ratio -- CI confidence intervals; Pancreatic cancer -- Cadmium -- Carcinogenesis -- Risk factors; Environmental protection -- Periodicals; Environmental health -- Periodicals; Environmental monitoring -- Periodicals; Environmental Monitoring -- Periodicals; Environnement -- Protection -- Périodiques; Hygiène du milieu -- Périodiques; Environnement -- Surveillance -- Périodiques; Environmental health; Environmental monitoring; Environmental protection; Periodicals; 333.705
• DOI: 10.1016/j.envint.2019.04.048
• Languages: English
• ISSNs: 0160-4120

Abstract

Abstract: Although profoundly studied, etiology of pancreatic cancer (PC) is still rather scarce. Some of established risk factors of PC are connected to an increased cadmium (Cd) body burden. Hence, the aim of this study was to investigate the role of this environmental pollutant in PC development by conducting human observational, experimental and in vitro studies. The case-control study included 31 patients with a histologically based diagnosis of exocrine PC subjected to radical surgical intervention as cases and 29 accidental fatalities or subjects who died of a nonmalignant illness as controls. Animal study included two treated groups of Wistar rats (15 and 30 mg Cd/kg b.w) and untreated control group, sacrificed 24 h after single oral exposure. In in vitro study pancreas hTERT-HPNE and AsPC-1 cells were exposed to different Cd concentrations corresponding to levels measured in human cancerous pancreatic tissue. Cd content in cancer tissue significantly differed from the content in healthy controls. Odds ratio levels for PC development were 2.79 (95% CI 0.91–8.50) and 3.44 (95% CI 1.19–9.95) in the third and fourth quartiles of Cd distribution, respectively. Animal study confirmed Cd deposition in pancreatic tissue. In vitro studies revealed that Cd produces disturbances in intrinsic pathway of apoptotic activity and the elevation in oxidative stress in pancreatic cells. This study presents three different lines of evidence pointing towards Cd as an agent responsible for the development of PC. Highlights: Malignant pancreas accumulates Cd. There is significant association between PC risk and Cd exposure. Oxidative stress induction is a possible mechanism of Cd carcinogenicity in pancreas. Disturbed apoptosis is a possible mechanism of Cd carcinogenicity in pancreas. Knowing of the patients' environmental history will allow risk stratification.