Epidemiology of Primary Liver Cancer in Serbia and Possible Connection With Cyanobacterial Blooms

Abstract

Today, the occurrence of harmful cyanobacterial blooms is a common phenomenon and a potential global health problem. Cyanobacteria can produce metabolites highly toxic to humans. More than 80% of reservoirs used for water supply in Central Serbia have bloomed over the past 80 years. A 10-year epidemiological study showed a significant increase in the incidence of primary liver cancer (PLC) in the regions where water from the blooming reservoirs was used for human consumption. At the same time, no correlation was found between the incidence of PLC and other risk factors, such as cirrhosis and hepatitis viruses. Given the strong association with PLC induction and various known possible mechanisms of carcinogenic action, it is highly possible that, cyanotoxins--acting as initiator and promoter--may be the major risk factor that acts synergistically with other risk factors to cause increased incidence of PLC. However, at present, it is still not certain whether cyanotoxins alone were sufficient to induce PLC. Therefore, additional assessment of the health risks that may arise from human exposure to cyanotoxins is advisable.

Review of 130 years of research on cyanobacteria in aquatic ecosystems in Serbia presented in a Serbian Cyanobacterial Database

“…MCs) from drinking water could present a risk factor for primary liver cancer and possibly even other types of cancer (Svirčev et al, 2010;Drobac, 2015). Epidemiological studies conducted in Serbia have revealed a significant correlation between an increased incidence of several cancers (brain; heart, mediastinum and pleural; ovarian; testicular; gastric; colorectal; retroperitoneal and peritoneal; leukemia; malignant skin melanoma; and primary liver cancer) and cyanobacterial blooms in reservoirs used for drinking water supply (Svirčev et al, 2009(Svirčev et al, , 2013b(Svirčev et al, , 2014bDrobac, et al 2011;Drobac, 2015).…”

Cyanobacteria and microcystin contamination in untreated and treated drinking water in Ghana

“…Their acute effetcs are primarily manifested in liver but MCs have been shown to induce gastrointestinal and renal damage or neurological symptoms as well (Manganelli et al, 2012). Chronic exposures to MCs have been linked to tumor promoting and carcinogenic effects which is based on laboratory animal and in vitro experiments (Svircev et al, 2010) and supported also by results of epidemiologic studies of human population consuming drinking water contaminated by these cyanotoxins (Fleming et al, 2002;Svircev et al, 2009Svircev et al, , 2013Svircev et al, , 2014Ueno et al, 1996;Yu et al, 1995;Zhou et al, 2002). In fact, MCs have been classified as possible human carcinogen (class 2B) by the International Agency for Research on Cancer (Grosse et al, ).…”

“…Chronic exposures to water contaminated with MCs at concentrations 1.1-3.28 µg L -1 have been linked with the increased incidence of colorectal cancer (Zhou et al 2002) or liver damage (Chen et al, 2009;Li et al, 2011) in China. In addition, there are reports on statistically significant associations between cyanobacterial blooms and non-alcoholic liver disease in USA (Zhang et al, 2015) or primary liver cancer in Serbia (Svircev et al, 2009(Svircev et al, , 2013(Svircev et al, , 2014.…”

Species- and congener-differences in microcystin-LR and -RR GSH conjugation in human, rat, and mouse hepatic cytosol

“…Chronic effects are more difficult to identify: information from epidemiological studies is scarce and inconclusive (IARC, 2006); MC-LR has been described to have tumor-promoting activity in animals (Nishiwaki-Matsushima et al, 1992) and on this basis classified as a 2B carcinogen by the International Agency for Research on Cancer (IARC, 2006). Some recent papers underlined the need of more attention on long-term MC-induced toxicity not only in the liver (Stipa et al, 2006;Chen et al, 2009;Metcalf and Codd, 2009;Li et al, 2011;Svircev et al, 2013).…”