Epidemiology and carcinogenesis of hepatocellular carcinoma

Abstract

The incidence of hepatocellular carcinoma (HCC) shows marked variation worldwide but the magnitude of this tumor is reflected by the occurrence of at least 1 million new cases annually and the uniformly dismal outlook with median survivals of <25 months after resection and <6 months with symptomatic treatment. The strikingly uneven distribution of this tumor parallels the prevalence of hepatitis B infection with rising incidence in western countries attributed to hepatitis C infection. Chronic hepatitis and cirrhosis constitute the major preneoplastic conditions in the majority of HCCs and may be related to other etiologic agents such as environmental chemical carcinogens including nitrites, hydrocarbons, solvents, organochlorine pesticides, and the chemicals in processed foods, cleaning agents, cosmetics and pharmaceuticals, as well as plant toxins such as anatoxins produced by fungi that cause spoilage of grain and food in the tropics. Genetic diseases such as genetic hematochromatosis, Wilson's disease, alpha-1-antitrypsin deficiency, and the inborn errors of metabolism including hereditary tyrosinemia and hepatic porphyria, are known to be associated with HCC. Numerous genetic alterations and the modulation of DNA methylation are recognized in HCC and it is likely that these genetic and epigenetic changes combine with factors involved in chronic hepatocyte destruction and regeneration to result in neoplastic growth and multiple molecular pathways may be involved in the production of subsets of hepatocellular tumors.

Blockade of four-transmembrane L6 family member 5 (TM4SF5)-mediated tumorigenicity in hepatocytes by a synthetic chalcone derivative #

“…24 Diverse extracellular cues, including growth factors, cytokines, and ECMs promote hepatocellular proliferation and migration/invasion. TM4SF5 expression appears to be regulated by transforming growth factor-␤ signaling (S. Choi and J.W.…”

Situs Inversus Totalis (SIT) with Hepatocellular Carcinoma (HCC): A Rare Case Report and Review of 12 Other Cases

“…Intermediate rates in Japan, Middle East and Mediterranean countries, and the lowest rates of 1-3 per 100,000 population for HCC are found in western countries, Australia, South America and India [2].…”

“…Rarely, liver cancer occurs in association with conditions that have a genetic, congenital or metabolic origin. HCC has been rarely documented in association with familial polyposis coli, ataxia telangiectasia, familial cholestatic cirrhosis, congenital hepatic fibrosis, neurofibromatosis, situs inversus and the fetal alcohol syndrome [2].…”

“…At least one million new cases of HCC occur annually and mortality from the disease remains high despite treatment. Cirrhosis has the most common association with HCC, being the underlying disease in 80 %-90 % of patients in most of the countries [2].…”

Bystin-like protein is upregulated in hepatocellular carcinoma and required for nucleologenesis in cancer cell proliferation

“…In these regions, the incidence is estimated to be 10-20 per 100 000 population [1]. Like many malignancies, HCC has characteristics of fast cell proliferation and tumor growth, metastasis at an early stage, and poor response to treatment.…”