Polymorphic variants of H-RAS protooncogene and their possible role in bladder cancer etiology

INTRODUCTION: H-RAS gene is a protooncogene encoding p21ras, a small protein with GTPase activity. This protein is a component of many signaling cascades, while mutations in H-RAS gene are often found in urinary bladder cancer and leads to continuous transmission of signals stimulating cancer cell growth and proliferation. The T81C polymorphism of H-RAS gene is a SNP, which, although does not seem to impair p21ras protein structure and function, may contribute to the development of bladder cancer. OBJECTIVES: The aim of our study was to characterize the prevalence and clinical significance of T81C polymorphism in patients with diagnosed bladder cancer. MATERIALS AND METHODS: 132 patients with diagnosed urinary bladder cancer were included in this study. The control group consisted of 106 healthy individuals. The experimental material was DNA, isolated from tumor tissue and peripheral blood lymphocytes. T81C polymorphism was detected using the MSSCP method and DNA sequencing. RESULTS: In the examined DNA samples, frequent polymorphic variations were found in codon 27 of H-RAS gene. In order to assess the clinical relevance of the polymorphism, the results were compared with those for the control group. The homozygous CC variant occurred more frequently in bladder cancer patients than in healthy individuals. CONCLUSIONS: DNA polymorphisms start to play an important role in evaluation of disease risk and progression. The occurrence of multiple variants of the same gene may contribute to differences in reactions to specific medications and sensitivity to carcinogens or DNA repair capacity. Our study demonstrated T81C polymorphism of H-RAS gene to have seemingly been associated with an increased risk of bladder cancer development.