Cadmium Exposure as a Putative Risk Factor for the Development of Pancreatic Cancer: Three Different Lines of Evidence

Abstract

Although profoundly studied, etiology of pancreatic cancer (PC) is still rather scant. Exposure to cadmium (Cd), a ubiquitous metal associated with well-established toxic and carcinogenic properties, has been hypothesized to one putative cause of PC. Hence, we analyzed recently published observational studies, meta-analyses, and experimental animal and in vitro studies with the aim of summarizing the evidence of Cd involvement in PC development and describing the possible mechanisms. Consolidation of epidemiological data on PC and exposure to Cd indicated a significant association with an elevated risk of PC among general population exposed to Cd. Cadmium exposure of laboratory animals was showed to cause PC supporting the findings suggested by human studies. The concordance with human and animal studies is buttressed by in vitro studies, although in vitro data interpretation is problematic. In most instances, only significant effects are reported, and the concentrations of Cd are excessive, which would skew interpretation. Previous reports suggest that oxidative stress, apoptotic changes, and DNA cross-linking and hypermethylation are involved in Cd-mediated carcinogenesis. Undoubtedly, a significant amount of work is still needed to achieve a better understanding of the Cd involvement in pancreatic cancer which could facilitate prevention, diagnosis, and therapy of this fatal disease.

The Hazardous Level of Heavy Metals in Different Medicinal Plants and Their Decoctions in Water: A Public Health Problem in Brazil

“…However, the consumption of more significant quantities of tea, four or more cups compared with 1 or less, may be detrimental to health. According to studies, cadmium induces cancers in animals and humans [44]. Cadmium toxicity affects photochemical and nutrient element composition of lettuce (Lactuca sativa L.) [45].…”

Hepatoprotective Effect of Oleuropein-Rich Extract from Olive Leaves against Cadmium-Induced Toxicity in Mice

“…Furthermore, Cd engenders oxidative stress in cells and macromolecules and results in severe pathologies and complications [5,24]. Several studies evoked the Cd toxicity mechanisms which could be related to the lipid peroxidation [9,25], the DNA expression epigenetic change [26], and the cellular transport pathway inhibition [27]. Moreover, its direct implication in oxidative stress by antioxidant enzyme affection suggests the utility of mineral antioxidants or nutriments such as polyphenols as a protective pathway against Cd toxicity [9].…”

Toxic-Metal-Induced Alteration in miRNA Expression Profile as a Proposed Mechanism for Disease Development

“…Our understanding of the importance of miRNAs in cancer development has increased over the last few decades. The International Agency for Cancer Research (IARC) has classified Cd as a human carcinogen with a well-established association to kidney and prostatic cancers [62] as well as considerable involvement in other cancers, such as pancreatic cancer [63][64][65] and thyroid cancer [66], among which the role of miRNA in Cd-induced carcinogenesis is of great value. Evidence supporting the toxic metal modification of miRNA expression and cancer development is increasing, with Cd and As being two primary mediators [60,67].…”