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.
Highlights
Pancreatic cancer (PC) is one of the most lethal human cancers and an important cause of cancer-associated-mortalities worldwide [1, 2]
Profound studies have been undertaken with the aim of improving our understanding of this aggressive disease, and while certain advances in molecular biology have greatly enhanced the understanding of PC pathogenesis, the etiology remains rather elusive
Human studies have been extended to include nonhuman species, such as mouse and livestock [53, 57]. Many of these organ deficits have been attributed to the actions of Cd and its ability to increase the generation of free radicals, alter cellular apoptosis [54], and promote epigenetic changes [58]
Summary
Pancreatic cancer (PC) is one of the most lethal human cancers and an important cause of cancer-associated-mortalities worldwide [1, 2]. The main nongenetic environmental factors that have been associated with PC initiation so far are inhalation of cigarette smoke, exposure to mutagenic nitrosamines, chlorinated hydrocarbon solvents, and heavy metals [4]. Attention must be given to involuntary human exposure to cadmium (Cd). This toxic element is currently one of the most abundant occupational and environmental pollutants; it is present in the diet, tobacco smoking, air, soil, and water [5]. Cadmium and its compounds have been classified as known human carcinogens by the International Agency for Research on Cancer since 1993 [13] based on epidemiological studies showing a causal connection with the development of lung cancer. This review will summarize, evaluate, and discuss information on Cd role in PC development collected from available and recently published observational studies, meta-analyses, experimental animal, and in vitro studies
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