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Gene–Environmental Interactions and Susceptibility to Liver Cancer

  • John B. ColerangleEmail author
Chapter

Abstract

Human liver cancer, specifically hepatocellular carcinoma (HCC), is the fifth most common malignancy worldwide and remains a major cause of cancer death. HCC accounts for over half a million deaths per year. Despite many efforts to understand the pathogenesis of HCC, little is known about its etiology. Hepatitis B and C, and aflatoxin B are the only established cause, and the proportion of cases of liver cancer attributed to Hepatitis B and C and aflatoxin B is about 75–80%. A family history of liver cancer accounts for only 3% of the cases of this disease. The remaining portions of cases are due to yet unrecognized factors. Alcohol is an important risk factor for the development of HCC since hepatic cirrhosis caused by chronic alcohol abuse has long been recognized as a major risk factor for the development of HCC. The pathogenesis of HCC is quite diverse and influenced by a variety of environmental and genetic factors of the host. The link between environmental factors, genetics, and the development of cancer has advanced our understanding of the factors that influence cancer risk. Understanding the relative roles of the environmental factors and genes in cancer etiology may clearly elucidate how each of these factors can disparately affect the health of individual members of a community. Although environmental, occupational, and recreational exposures to carcinogens contribute to cancer risk in humans, variation in incidence and progression of cancer in a population is due to genetic polymorphisms in the population. Functional polymorphisms that influence an individual’s susceptibility to liver cancer include gene products involved in activation and detoxification of carcinogens and DNA repair. Gene polymorphisms that play key roles in apoptosis may also provide insight to individual susceptibility to liver cancer. Thus genetic polymorphisms may explain why individuals with shared environmental exposures do not always share cancer morbidity and mortality.

Keywords

Hepatocellular carcinoma (HCC) Hepatitis B and C Aflatoxin B Alcohol Functional polymorphisms in genes involved in activation and detoxification of carcinogens and DNA repair Influence an individual’s susceptibility to liver cancer 

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  1. 1.Sanofi-Aventis PharmaceuticalsRegulatory Pharmacology and Toxicology – USBridgewaterUSA

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