Green tea consumption: A potential chemopreventive measure for hepatocellular carcinoma?

Hepatocellular carcinoma (HCC) is a major global health problem. HCC is the sixthmost common incident cancer and the fourth-leading cause of cancer death in 2015. HCC is more common in men; 1 in 45 men and 1 in 113 women develop liver cancer before age 79 years in the world. HCC is a highly lethal cancer given that a majority of patents with HCC are diagnosed in noncurative stages. Although patients with early-stage HCC are eligible for potentially curative treatment, up to 70% of patients who receive curative resection or local ablation eventually develop recurrent tumors within 5 years. There are no effective chemopreventive strategies for these patients and those at risk for HCC development. In order to decrease the burden of HCC mortality, it is crucial to identify high-risk groups of patients and provide interventions to decrease the risk of tumor development and recurrence after curative treatment. Prognostic biomarkers should provide information to identify such high-risk patients. Serum alfafetoprotein (AFP) is a well-established diagnostic and prognostic biomarker for HCC. Although highly elevated serum AFP predicts a poor clinical outcome, therapeutic implications of an elevated AFP in HCC patients remain unclear. Similarly, several other proteomic or genomic biomarkers aid in diagnosis and correlate with prognosis; however, they remain underutilized because of lack of wide availability. For example, with recent technical advances in genomics and transcriptomics, researchers used genome-wide expression profiling of liver cancer and adjacent benign tissues and showed that the gene expression pattern of tissue adjacent to the tumor predicts clinical outcome in HCC patients after surgical resection. Although this gene expression signature provides prognostic information, it does not provide biological information amenable to interventions that may improve clinical outcomes. More recently, sorafenib was tested as an adjuvant treatment, but failed to prolong recurrent free survival following curative surgical resection or local ablation in a large, phase 3, double-blind, placebo-controlled trial. Identification of mechanism-based prognostic biomarkers that can be intervened to improve the clinical outcomes is a critical unmet need in HCC research. In the current issue of HEPATOLOGY, Fu et al. have published their research examining the utility of an exocyclic deoxyguanosine DNA adduct, gammahydroxy-1,N-propanodeoxyguanosine (c-OHPdG), in three mouse models of hepatocarcinogenesis and its utility as a prognostic biomarker with further validation in human HCC samples. c-OHPdG is one of the most common lipid peroxidation–derived DNA adducts that can modify DNA bases, including p53 genes, and it frequently causes G to T and G to A mutations. It is a well-established mutagen in smoking-induced lung cancer. However, the role of cOHPdG in HCC has not been investigated in the past. The investigators showed that c-OHPdG levels increase with age in nucleotide excision repair-deficient mice (Xpa) and the whole-liver levels correlated with Abbreviations: AFP, alfa-fetoprotein; CI, confidence interval; c-OHPdG, gamma-hydroxy-1,N-propanodeoxyguanosine; HCC, hepatocellular carcinoma.