Alterations Of P53, Rb, RARβ And MUC1 Protein Expression In Esophageal Carcinomas And Genetic Polymorphisms Of XRCC1: A Comparative Study Between The Young And Old Patients At High-incidence Area For Esophageal Cancer In Henan

Esophageal carcinoma (EC) is one of the six most common malignant diseases in the world, with a remarkable geographical distribution, the ratios of incidence between the high- and low-incidence area could be as high as 500:1 for EC. Linzhou and nearby counties in Henan province, is one of the highest incidence and mortality areas for EC in China and in the world. Through mass survey and follow-up study for the past fifty years, it has been recognized that esophageal carcinogenesis is a multistage and progressive process involved by multiple genetic changes and risk factors. Although EC usually occurs in old patients ( 50 years old), the young EC patients ( 40 years old) have been frequently identified and the incidence seems increasing in recent years. The young EC patients have been characterized by more poorly differentiated EC type and a poor prognosis because of early diffuse inflltrative growth and vassel invasion, the 5-year survival rates is lower than that of their older counterpart. These phenomena increase many academic questions, eg, what is the mechanism to push the youth to develop EC much earlier than the old even with the same life-style and similar environment? What is the molecular basis for the high susceptibility of the young patients Both environmental and genetic factors may play an important role in the development of EC for the young patients. The activation of oncogenes and inactivation of tumor suppressor genes may be the key molecular changes for esophageal carcinogenesis. The alteration of p53-Rb system has been observed as important molecular events with the highest frequency during the esophageal carcinogenesis for the middle and old patients at high-incidence area in Henan. RARB may play an important role in many different types of tumors by regulating cell growth inducing differentiation and apoptosis. MUC1 is a anti-adhesion molecule and expression has been observed in many different kinds of human tumors. MUC1 may play a role in inhibiting cancer cell adhesion and metastasis. However, the similar information for the molecular changes mentioned above is very limited in young EC patients.It has been well known that individual variation is an apparent factor influencing EC. In Henan, the young EC patients may occur about 10 years earlier than the old patients who share the same area and similar environment, which indicating the importance of individual genetic susceptibility in young EC patients. XRCC1 gene is an important DNA repair gene. XRCC1 26304TT genotype has been reported to be associated with elevated risk for EC, but polymorphisms analysis on XRCC1 gene in young EC patients has not been reported.To further characterize the molecular basis of esophageal carcinogenesis in young EC patients, the present study was undertaken to determine the alternations of P53, Rb, RARI3 and MUC1 expression and genetic polymorphisms of XRCC1 in esophageal cancer tissue and blood samples from young and old EC subjects, to determine the difference in molecular changes between the young and old patients, and to provide the theoretical basis and strategies for clinical biotherapy and preventions.1.2.1 Material and MethodSeventy-two young EC patients (=40 years old) and seventy-three old EC patients ( 50 years old) were enrolled from Linzhou City Hospital, Yaocun Esophageal Cancer Hospital and Anyang City Tumor Hospital, the high-incidence areas for EC in Henan. The young healthy controls ( 40 years old, n=62) were volunteers from the same areas. All the patients were not treated either by chemotherapy or by radiotherapy before operation. All surgically resected specimens were fixed with 85% ethanol, paraffin embedded, and serially sectioned for histopathological diagnosis, immunohistochemical analysis and DNA extracting. Blood samples were drawn from the young healthy controls and the old patients, stored in the liquid nitrogen in the field and then transferred in a -80 癈 freezer for DNA extracting. Immunohistochemistry(ABC method) and PCR-RFLP were applied to determine the...