Epidemiology of Cancers in Serbia and Possible Connection with Cyanobacterial Blooms

Abstract

Cyanobacteria produce toxic metabolites known as cyanotoxins. These bioactive compounds can cause acute poisoning, and some of them may promote cancer through chronic exposure. Direct ingestion of and contact with contaminated water is one of the many exposure routes to cyanotoxins. The aim of this article was to review the incidence of 13 cancers during a 10-year period in Serbia and to assess whether there is a correlation between the cancer incidences and cyanobacterial bloom occurrence in reservoirs for drinking water supply. The types of cancers were chosen and subjected to epidemiological analyses utilizing previously published data. Based on the epidemiological and statistical analysis, the group of districts in which the incidences of cancers are significant, and may be considered as critical, include Nišavski, Toplički, and Šumadijski district. A significantly higher incidence of ten cancers was observed in the three critical districts as compared to the remaining 14 districts in Central Serbia. These elevated incidences of cancer include: brain cancer, heart, mediastinum and pleura cancer, ovary cancer, testicular cancer, gastric cancer, colorectal cancer, retroperitoneum and peritoneum cancer, leukemia, malignant melanoma of skin, and primary liver cancer. In addition, the mean incidence of five chosen cancers was the highest in the three critical regions, then in the rest of Central Serbia, while the lowest values were recorded in Vojvodina. Persistent and recurrent cyanobacterial blooms occur during summer months in reservoirs supplying water to waterworks in the three critical districts. People in Central Serbia mainly use surface water as water supply (but not all the water bodies are blooming) while in Vojvodina region (control region in this study) only groundwater is used. Among the 14 "noncritical" districts, reservoirs used for drinking water supply have been affected by recurrent cyanobacterial blooms in two districts (Rasinski and Zaječarski), but the waterworks in these districts have been performing ozonation for more than 30 years. We propose that the established statistical differences of cancer incidences in Serbia could be related to drinking water quality, which is affected by cyanobacterial blooms in drinking water reservoirs in certain districts. However, more detailed research is needed regarding cyanobacterial secondary metabolites as risk factors in tumor promotion and cancerogenesis in general.

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).…”

Toxic cyanobacteria and cyanotoxins in European waters – recent progress achieved through the CYANOCOST Action and challenges for further research

“…Recent reviews on human and animal health aspects include: a health review chapter (Codd et al, 2017), an epidemiological assessment of cancers in Serbia with reference to cyanobacterial blooms (Svirčev et al, 2014a), a review of production, toxinology and toxicology of the ANTX-a and STX neurotoxins (Testai et al, 2016) and a review on epidemiological investigations on health issues related to cyanotoxins (Svirčev et al, 2017a). Recently reported animal intoxications involving cyanobacterial blooms and cyanotoxins have included dogs in the Netherlands, with hANTX-a (Faassen et al, 2012b) and MC-LR (Lürling and Faassen, 2013) as likely proximal causes.…”

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.…”