Study On Molecular Basis Of Genetic Susceptibility And Carcinogenesis Of Esophageal Cancer

Esophageal cancer (EC) is one of the most common malignant tumors and the second leading cause among all tumor deaths in China. Previous studies in our laboratory showed that the genetic susceptibility to EC was one of the important causes for the high occurence and familial gathering of this malignancy in some areas of Northern China. So it is of great significance to tumor prevention to reveal the mechanisms of the genetic susceptibility and establish effective ways of screening susceptible individuals. Additionally, squamous cell cancer is a major type among a variety of ECs. It takes several stages to develop from normal squamous cell epithelium of the esophagus to advanced-stage squamous cell EC. Little was known about alterations of genes involved in the different stages.Inactivation of the p53 tumor suppressor gene is turning out to be the most common genetic alteration in human tumors. Mutations of the p53 gene have been detected in a variety of tumors including EC. The alterations of this gene were found to correlate with specific stages during the development of several tumors. Furthermore, p53 mutations were also detected in normal and malignant tissues from members of some hereditary cancer families. All these findings suggested that p53 mutations could be not only involved in somatic cells, contributing to cell transformation, but also inherited, as the genetic basis of the cancer susceptibility in members of some cancer families. Recently, MDM2 gene (a cellular oncogene) product was found to form a complex with p53 protein and inhibit its negative regulation of cell growth and division. Meanwhile, amplification or overexpression of this gene, bringing about the similar effects with p53 mutations, were detected in some tumor tissues. Since 1980s, it has been widely accepted that c-myc and c-ki-ras2 genes take important roles in cell proliferation and differentiation and can be activated respectively by amplifications of c-myc gene and gain-of-function mutations of c-ki-ras2 gene, leading to cell growth out of control.Based on all aforementioned data and ideas, we investigated aletrations of...