Cyanotoxin exposure and hepatocellular carcinoma

Abstract

Cyanobacteria are ubiquitous in aquatic and terrestrial environments worldwide and include a number of species producing tumor-promoting hepatotoxins. Human exposure to cyanobacteria and cyanotoxins primarily occurs though ingestion of contaminated drinking water and food sources. In a Northeast U.S. population, we recently reported an independent association of oral cyanobacteria with risk of hepatocellular carcinoma (HCC). In a cross-sectional study of 55 HCC patients in Hawaii, U.S.A., serum microcystin/nodularin (MC/NOD), cylindrospermopsin (CYN), and anabaenopeptin (AB) were measured by ELISA. In a subset of 16 patients, cyanotoxin levels were compared by tumor expression of over 700 genes analyzed via the Nanostring nCounter Fibrosis panel. MC/NOD, CYN, and AB were detected in all HCC patients. MC/NOD and CYN levels significantly varied by etiology with the highest levels in cases attributed to metabolic risk factors, specifically, hyperlipidemia, type 2 diabetes, and non-alcoholic fatty liver disease/non-alcoholic steatohepatitis. Cyanotoxin levels were significantly positively correlated with tumor expression of genes functioning in PPAR signaling and lipid metabolism. Our study provides novel albeit limited evidence that cyanotoxins may a role in the pathogenesis of HCC through the dysregulation of lipid metabolism and progression of hepatic steatosis.