Environmental cadmium exposure and pancreatic cancer: Evidence from case control, animal and in vitro studies

Vladimir R. Djordjevic, David R. Wallace, Amie Schweitzer, Novica Boricic, Djordje Knezevic, Slavko Matic, Nikola Grubor, Mirko Kerkez, Dejan Radenkovic, Zorica Bulat, Biljana Antonijevic, Vesna Matovic, Aleksandra Buha

Research output: Contribution to journalArticlepeer-review

99 Scopus citations


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.

Original languageEnglish
Pages (from-to)353-361
Number of pages9
JournalEnvironment International
StatePublished - Jul 2019


  • Cadmium
  • Carcinogenesis
  • Pancreatic cancer
  • Risk factors


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