| Prostate cancer is the third most common cancer in men, but its etiology is still not clear. There is significant racial/ethnic difference in the incidence of prostate cancer, which is caused by many factors, including genetic susceptibility and environmental factors. In human, there are two kinds of steroid 5-re-ductase, type II is encoded by SRD5A2 gene, and is mainly located in genital skin and prostate tissue, regulating the growth and differentiation of prostate. There are two common single nucleotide missense polymorphisms in SRD5A2 gene, V89L and A49T. The V89L substitution leads to a 30% decrease of the steroid 5-reductase activity, while the activity of the A49T mutant enzyme increases by 5 times than that of the wild type. It has been reported that these two polymorphisms may be associated with development and progress of prostate cancer. Transforming growth factor-β1TGF-β1) is a polypeptide growth factor, which is encoded by the TGF-β1 gene. The gene mutations of the molecules in the TGF-β1 signaling pathway play an important role in the genesis of many diseases , including cancer. In prostate cancer cells, there are some defects in the TGF-β1 signaling pathway, and restoration of this pathway in prostate cancer cells can suppress in vitro tumor growth by inhibiting cell proliferation. In addition, TGF-β1 inhibits the cell growth and increases the production of type I collagen , suggesting the involvement of TGF-β1 in prostatic enlargement as a modulator of the extracellular matrix. Thus, alternations in the TGF-β1, gene might be involved in the development of prostate cancer and benign prostatic hyperplasia.The TGF-β1 gene codonlO polymorphism resultis in the replacement of a leucine with a proline, altering the ability of signal peptide to direct protein transport across the endoplasmic reticulum, as a result, the expression and func-tion of TGF- is changed. This gene polymorphism has been reported to be associated with several diseases. In this study, using a case-control design, we analyzed the SRD5A2 gene A49T and V89L polymorphisms and codonlO polymorphism of TGF, gene in a native Japanese population to clarify their roles in prostate cancer and benign prostate hyperplasia.There two parts in this study: 1. Detection of the SRD5A2 gene A49T and V89L polymorphisms in prostate cancer patients, benign prostate hyperplasia patients and male controls. 2. Detection of the codonlO polymorphism of TGF gene in prostate cancer patients, benign prostate hyperplasia patients and male controls. The relationships between these gene polymorphisms and disease susceptibility , and the disease status of prostate cancer were analyzed.Materials and Methods1. Subjects; A total of 773 subjects consisting of 302 prostate cancer patients , 228 benign prostatic hyperplasia patients, and 243 male controls were enrolled in the study of SRD5A2 gene polymorphisms. A total of 873 subjects consisting of 351 prostate cancer patients, 221 benign prostatic hyperplasia patients , and 303 male controls were enrolled in the study of TGF gene polymorphism. The male control group was composed of volunteers who attended the yearly health check-up.Pathological grading of the prostate cancer was determined according to the General Rule for Clinical and Pathological Studies on Prostate Cancer by the Japanese Urological Association and the Japanese Society of Pathology, which is mainly based on the WHO criteria and Gleason score. The clinical or pathological stage was obtained by the review of the medical records and categorized using the Tumor-Node-Metastasis system and the Whitmore-Jewett system.2. Materials:Main instruments-. ABI PRISM?310 Gene Analyzer, electrophoresis apparatus, PCR amplification system, cryogenic refrigerator, incubator, pressure sterilizer, high-speed and low-temperature centrifuger, mixing system, pipettor.Main regents; agarose gel, 10 x PCR buffer, 25mM MgCl2, 2mM dNTP,Ampli-Taq Gold DNA polymerase, ABI PRISM BigDye?Terminator Cycle Sequencing kits, QIA...
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