Hepatocellular Carcinoma: Epidemiology and Molecular Carcinogenesis

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Abstract

Primary liver cancer, which consists predominantly of hepatocellular carcinoma (HCC), is the fifth most common cancer worldwide and the third most common cause of cancer mortality. HCC has several interesting epidemiologic features including dynamic temporal trends; marked variations among geographic regions, racial and ethnic groups, and between men and women; and the presence of several well-documented environmental potentially preventable risk factors. Moreover, there is a growing understanding on the molecular mechanisms inducing hepatocarcinogenesis, which almost never occurs in healthy liver, but the cancer risk increases sharply in response to chronic liver injury at the cirrhosis stage. A detailed understanding of epidemiologic factors and molecular mechanisms associated with HCC ultimately could improve our current concepts for screening and treatment of this disease.

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Most cited references 181

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Liver fibrosis.

Ramón Bataller, David A Brenner (2005)

Liver fibrosis is the excessive accumulation of extracellular matrix proteins including collagen that occurs in most types of chronic liver diseases. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension and often requires liver transplantation. Our knowledge of the cellular and molecular mechanisms of liver fibrosis has greatly advanced. Activated hepatic stellate cells, portal fibroblasts, and myofibroblasts of bone marrow origin have been identified as major collagen-producing cells in the injured liver. These cells are activated by fibrogenic cytokines such as TGF-beta1, angiotensin II, and leptin. Reversibility of advanced liver fibrosis in patients has been recently documented, which has stimulated researchers to develop antifibrotic drugs. Emerging antifibrotic therapies are aimed at inhibiting the accumulation of fibrogenic cells and/or preventing the deposition of extracellular matrix proteins. Although many therapeutic interventions are effective in experimental models of liver fibrosis, their efficacy and safety in humans is unknown. This review summarizes recent progress in the study of the pathogenesis and diagnosis of liver fibrosis and discusses current antifibrotic strategies.

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Overweight, Obesity, and Mortality from Cancer in a Prospectively Studied Cohort of U.S. Adults

Eugenia E Calle, Carmen Rodríguez, Kimberly Walker-Thurmond … (2003)

The influence of excess body weight on the risk of death from cancer has not been fully characterized. In a prospectively studied population of more than 900,000 U.S. adults (404,576 men and 495,477 women) who were free of cancer at enrollment in 1982, there were 57,145 deaths from cancer during 16 years of follow-up. We examined the relation in men and women between the body-mass index in 1982 and the risk of death from all cancers and from cancers at individual sites, while controlling for other risk factors in multivariate proportional-hazards models. We calculated the proportion of all deaths from cancer that was attributable to overweight and obesity in the U.S. population on the basis of risk estimates from the current study and national estimates of the prevalence of overweight and obesity in the U.S. adult population. The heaviest members of this cohort (those with a body-mass index [the weight in kilograms divided by the square of the height in meters] of at least 40) had death rates from all cancers combined that were 52 percent higher (for men) and 62 percent higher (for women) than the rates in men and women of normal weight. For men, the relative risk of death was 1.52 (95 percent confidence interval, 1.13 to 2.05); for women, the relative risk was 1.62 (95 percent confidence interval, 1.40 to 1.87). In both men and women, body-mass index was also significantly associated with higher rates of death due to cancer of the esophagus, colon and rectum, liver, gallbladder, pancreas, and kidney; the same was true for death due to non-Hodgkin's lymphoma and multiple myeloma. Significant trends of increasing risk with higher body-mass-index values were observed for death from cancers of the stomach and prostate in men and for death from cancers of the breast, uterus, cervix, and ovary in women. On the basis of associations observed in this study, we estimate that current patterns of overweight and obesity in the United States could account for 14 percent of all deaths from cancer in men and 20 percent of those in women. Increased body weight was associated with increased death rates for all cancers combined and for cancers at multiple specific sites. Copyright 2003 Massachusetts Medical Society

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Global cancer statistics in the year 2000.

D M Parkin (2001)

Estimation of the burden of cancer in terms of incidence, mortality, and prevalence is a first step to appreciating appropriate control measures in a global context. The latest results of such an exercise, based on the most recent available international data, show that there were 10 million new cases, 6 million deaths, and 22 million people living with cancer in 2000. The most common cancers in terms of new cases were lung (1.2 million), breast (1.05 million), colorectal (945,000), stomach (876,000), and liver (564,000). The profile varies greatly in different populations, and the evidence suggests that this variation is mainly a consequence of different lifestyle and environmental factors, which should be amenable to preventive interventions. World population growth and ageing imply a progressive increase in the cancer burden--15 million new cases and 10 million new deaths are expected in 2020, even if current rates remain unchanged.