POLYMORPHISMS OF HPC2/ELAC2 AND SRD5A2 (5α-Reductase Type II) GENES IN PROSTATE CANCER

ABSTRACT Prostate cancer is the proliferation of malignant cells in the prostate gland. The HPC2/ELAC2 gene on chromosome 17p11.2 and SRD5A2 gene on chromosome 2p22-23 are predisposing genetic factors. We examined the relationship between Ser217Leu and Ala541Thr polymorphisms of the former gene, and Ala49Thr and Val89Leu polymorphisms of the latter gene to prostate cancer in Turkish men, using the polymerase chain reaction (PCR) method and appropriate restriction enzymes. The HPC2/ ELAC2 gene Ser217-Leu and SRD5A2 gene Ala49Thr polymorphisms were associated with an increased risk of prostate cancer in Turkish men [for the HPC2/ELAC2 gene Ser217Leu polymorphism: odds ratio (OR) 2.7; confidence interval 95% (CI 95%) 1.6-4.8; p 0.000<0.05, and for the SRD5A2 gene Ala49Thr polymorphism: OR 2.4; CI 95% 1.2-4.9; p 0.004<0.05]

Autophagy to Survive

Autophagy is the catabolic mechanism that involves cell degradation of unnecessary or dysfunctional cellular components through the actions of lysosomes. It helps to keep the cells alive in such cases like oxidative stress, lack of nutrients and growth factors providing recycling of intracellular molecules. However, it works as a part of metabolism regulation, morphogenesis, cell differentiation, senescence, cell death and immune system. As a result of impairment of this mechanism, pathological situations arise including cancer, neurodegenerative and infectious diseases. Consequently, researches about autophagy mechanism are important for the development of novel diagnosis, follow-up and treatment modalities in health problems. [Archives Medical Review Journal 2014; 23(3.000): 411-419

Interindividual Difference in CYP2A6 Genotypes as Determined with Restrictional Fragment Length Polymorphism in Relation to GSTM1 and GSTT1 Genes Among the Patients with Prostate Carcinoma

3rd Asian Pacific Regional Meeting of the International-Society-for-the-Study-of-Xenobiotics -- MAY 10-12, 2009 -- Bangkok, THAILANDWOS: 000269483300052…Int Soc Study Xenobio

Interindividual Difference in CYP2A6 Genotypes as Determined with Restrictional Fragment Length Polymorphism in Relation to GSTM1 and GSTT1 Genes Among the Patients with Prostate Carcinoma

3rd Asian Pacific Regional Meeting of the International-Society-for-the-Study-of-Xenobiotics -- MAY 10-12, 2009 -- Bangkok, THAILANDWOS: 000269483300052Int Soc Study Xenobio

SIRT1 gene polymorphisms affect the protein expression in cardiovascular diseases.

Cardiovascular disease (CVD), the leading cause of death worldwide, is related to gene-environment interactions due to epigenetic factors. SIRT1 protein and its downstream pathways are critical for both normal homeostasis and protection from CVD-induced defects. The aim of this study was to investigate the association between SIRT1 single nucleotide polymorphisms (SNPs) (rs7895833 A>G in the promoter region, rs7069102 C>G in intron 4 and rs2273773 C>T in exon 5 silent mutation) and SIRT1 and eNOS (endothelial nitric oxide synthase) protein expression as well as total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) in CVD patients as compared to controls. The frequencies of mutant genotypes and alleles for rs7069102 and rs2273773 were significantly higher in patients with CVD compared to control group. The risk for CVD was increased by 2.4 times for rs7069102 and 1.9 times for rs2273773 in carriers of mutant allele compared with carriers of wild-type allele pointing the protective role of C allele for both SNPs against CVD. For rs7895833, there was no significant difference in genotype and allele distributions between groups. SIRT1 protein, TAS, TOS and OSI levels significantly increased in patients as compared to control group. In contrast, level of eNOS protein was considerably low in the CVD patients. An increase in the SIRT1 expression in the CVD patients carrying mutant genotype for rs7069102 and heterozygote genotype for all three SNPs was observed. This is the first study reporting an association between SIRT1 gene polymorphisms and the levels of SIRT1 and eNOS expressions as well as TAS, TOS and OSI

Investigation of p53 Tumor Suppressor Gene Mutations in Patients with a Lung Mass Using Sequence Analysis

WOS: 000284798000003Objective: The p53 tumour suppressor gene plays an important role in the regulation of cell proliferation. It is located on the short arm of the 17th chromosome. It has 11 exons and encodes for a tumor suppressor protein called p53 which is 53kD in weight and 393 amino acids in length. This protein, a transcription factor, is an important regulator of cell cycle. Up to date, a number of mutations (75% of which are found between codon 26 and 332) have been detected on p53 gene. Recent researches showed that lung neoplasm resulting from the mutations of p53 gene varied between 33% (adenocarcinoma) and 70% (small cell lung cancer), and it is reported that the hot spots were mainly found at the codons 175, 248, and 273. Material and Methods: In this study, the exons, exonintron junctions, and some intron regions, which are located between exon 4-9 of p53 gene, of 24 patients who had a surgical operation due to a lung mass were examined by automatic DNA sequencing in University of Leipzig. Results: 53 missense and 7 frameshift mutations were detected between 4(th) and 9(th) exons (Codons 36-318) of 18 samples among the 24 samples. Fifty five of these mutations were heterozygous, and five of them were homozygous. Similarly, 12 missense mutations detected as a result of the serial analyses of the region between introns 4-9, and seven of them were heterozygous and 5 were homozygous. Conclusion: Some research regarding p53 gene reported that codon 175, 248, and 273 were hot spots and mutations were frequent in these codons. However we have not seen any mutations in any of these codons in our study. Nucleotide changes at the positions 13432 (5' beginning) and 13999 (3' ending) of 6th intron, which are very important regions, may result in the formation of an abnormal protein. We suppose that other nucleotide changes are not very important due to their heterozygous nature and location.Cukurova UniversityCukurova University [TF.2000-M-17]We would like to thank director of Human Genetics Institution Professor Ursula G. Froster from Faculty of Medicine, Leipzig University, and their research committee for their contributions. This project was supported by the Cukurova University Research Grant TF.2000-M-17

Comparison of rs7895833 A>G, rs7069102 C>G and rs2273773 C>T SNPs with SIRT1 and eNOS protein levels.

<p>n: number of individuals. Statistical evaluation by the Student’s t-test. The results are shown as mean±Standart Deviation (SD).</p><p>*p<0.05.</p