ABSTRACT
The results of the whole-exome DNA sequencing of eight prostate adenocarcinoma patients are presented. DNA was isolated from the peripheral blood as well as healthy and tumor prostate tissue from each patient. Bioinformatics analysis was conducted and the most significant mutations in prostate cancer patients were revealed. The obtained data could be important for understanding of the molecular mechanisms of prostate cancer pathogenesis and facilitate development of new approaches for treatment of the disease.
Subject(s)
Exome Sequencing , Mutation , Prostatic Neoplasms/genetics , Humans , Male , Prostatic Neoplasms/pathologyABSTRACT
MicroRNAs (MiRNAs) act as key post-transcriptional regulators of gene expression. This review examines current advances in the study of the role of miRNAs in cancer, including prostate cancer. Issues devoted to the nomenclature, biogenesis, the role of miRNAs as oncogenes and tumor suppressors, and their role in the diagnosis, treatment, and prognosis of prostate cancer are discussed. Assessment ofthe role of miRNAs in the development of prostate cancer will promote early diagnosis and will be important for the development of new approaches to the disease treatment.
Subject(s)
MicroRNAs , Prostatic Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Genes, Tumor Suppressor , Humans , Male , MicroRNAs/genetics , Neoplasms/genetics , Prognosis , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/pathologyABSTRACT
We examined the correlations between the polymorphic alleles of the DNA repair genes XRCC1 (c.839G> A, rs25489; and c.1196A> G, rs25487), XPA (c.-4A> G, rs1800975), and XPD (c.2251A> C, rs13181) and the progression and severity of neoplasias in the bladder and kidney in patients of three distinct ethnic groups, Bashkir, Russians, and Tatar, residing in the Republic of Bashkorostan. The study enrolled 468 cancer patients and 351 healthy individuals. Genotyping for polymorphic alleles was carried out using the PCR-RFLP method. We identified a correlation between allele A of the c.839 G>A locus of the XRCC1 gene and the incidence of the bladder cancer (BC) and kidney cancer (KC) in the Tatar study group, using the additive genetic effects model (Odds Ratio (OR) = 5.23 and OR = 3.90). In turn, the heterozygous G/A genotype was present at a significantly higher frequency in the KC patients of Bashkir ethnic origin, compared with the control group (p = 0.0061, OR= 4.72). Additional analysis with consideration of participants' smoking status showed that the G/A genotype is significantly more frequent in smokers with BC (OR = 1.96, p = 0.05) then in healthy smokers. We also determined, using the recessive genetic model, that the genotype A/A of the c. 1196A>G locus of the XRCC1 gene was correlated with a higher risk of BC in the Russian cohort (OR = 2.29, p = 0.0082) and an increased incidence of KC in the Bashkir group (OR = 4.06, p = 0.05). A similar correlation was obtained for smokers. In contrast, the allele c.2251 A>C in the XPD gene correlated with a lower risk for BC and KC in the Tatars (p = 0.0003, OR = 0.48 and p < 0.0001, OR = 0.37) in the additive model and in the Bashkirs (p = 0.0083, OR = 0.12) and Russians (p = 0.0001, OR = 0.14) in the recessive model. Further, we uncovered that polymorphism c.839 G>A in the XRCC1 gene contributes to the progression of noninvasive and invasive BC and promotes KC at early and advanced stages of the disease. Thus, we identified similar correlations between DNA repair gene polymorphism and the incidence and progression of BC and KC. We propose that this result points to the involvement of common pathogenetic mechanisms in the initiation and progression of the urinary neoplasias.
