Long-term Exposure to Cadmium in Food and Cigarette Smoke, Liver Effects and Hepatocellular Carcinoma

Rising incidence of hepatocellular carcinoma (HCC) has been noted in recent years along with diabetes for which reasons and mechanisms are unclear. The rise in HCC is attributed to increasing rates of hepatitis C virus (HCV) infections while increases in diabetes are attributed to obesity. Increased HCC risk has also been noted in diabetes and obesity. Cadmium, a common food contaminant and a constituent of cigarette smoke, is one of ten chemicals considered by the World Health Organization to be of major public health concern. A correlation of cadmium intakes and increased HCC mortality risk has been noted in an ecological study while both hepatocellular carcinoma and hepatic adenoma occurred in cadmium-exposed mice. In the U.S. NHANES III, urinary cadmium levels, indicative of long-term exposure, have been associated with pre-diabetes and diabetes in a dose dependent manner. Intriguing possibility is that cadmium may increase HCC risk through increasing the frequency of hepatogenous diabetes. Overall aim of the present review is to explore if cadmium is a relevant risk factor in chronic liver disease and a rising HCC incidence. It will highlight cadmium levels detectable in various foods, livers, kidneys and urine samples of humans together with global health threat of ingested cadmium, pointing to measures for reducing exposure and a need for revision of guidelines for safe intake levels. Lastly, it will examine evidence for potential roles of cadmium in chronic liver diseases and HCC risk in a call for human case-control studies and animal experiments to elucidate underlying molecular mechanisms. Keywords: Cadmium, Cytochrome P450, Chronic inflammation, Food contaminants, Hepatocellular carcinoma, Hepatocarcinogens, Hepatogenous diabetes, Obesity, Type-2 diabetes, human case-control studies