Investigation of CASP8 and CASP9 gene polymorphisms in breast cancer patients

ABSTRACTINVESTIGATION OF CASP8 AND CASP9 GENE POLYMORPHISMS IN BREAST CANCER PATIENTSAsuman ÇELEBİMaster of Science Thesis, Department of Medical Biology and GeneticSupervisor Asist. Prof. Dr. Recep ERÖZDecember 2011, 71 pagesBreast cancer is the most common type of cancer in women among all types of cancer. Inherited mutations and alterations in cancer susceptibility genes constitute %5-10 of risk factors that cause breast cancer. Some of the changes in cancer susceptibility genes come into being during the process of the apoptosis mechanism. Apoptosis (programmed cell death) also known as suicide of cells is physiological event which is responsible for tissue homeostasis. In stage of triggering of mechanism of apoptosis or alterations in any step of apoptosis could promote development of tumor tissue. A large family of cystein proteases, termed caspases, is responsible for the execution of apoptosis in higher eucaryotes. It has been identified in previous studies that D302H polymorphism of CASP8 gene effect the formation of breast cancer, but as far as we know it was not found information for the relationship between breast cancer and Q221R G>A, 83 C/T and 5969 C/T polymorphisms of CASP9 gene. This study was planned to investigate the relationship between risk of breast canser and mentioned polymorphisms of CASP8 (D302H) and CASP9 (Q221R G>A, 83 C/T, 5969 C/T) genes which play important role during cell death. For this aim, in our study, paraffin-embedded tissue samples belonging to 55 patients who had been operated by diagnosed breast cancer and 32 healthy induviduals who had been operated caused of non-breast cancer was studied. After the isolation of DNA from this individuals? paraffin-embedded tissue samples, PCR-RFLP method was applied for investigation of related polimorphisms. C allele of CASP8 gene, D302H polymorphism, was found to be associated with a reduced risk of breast cancer (p:0.067). C allele of 83 C/T polymorphism (p:0.000) and T allele of 5969 C/T polymorphism (p:0.000) of CASP9 gene was found to have a protective effect towards breast cancer. But not found to be associated with breast cancer risk and CASP9 gene Q221R G/A polymorphism.Key words: Breast cancer, CASP8, CASP9, Polymorphism