RESUMO
The role of the cytochrome P450 1A2 (CYP1A2) rs2472299, rs2470890 and rs11072508 polymorphisms in prostate cancer risk, disease progression and tumour development remains unclear. The potential associations of these three CYP1A2 polymorphisms and haplotypes with prostate cancer susceptibility and its clinicopathological characteristics were therefore investigated. The present case-control study consisted of 522 patients with prostate cancer and 554 healthy controls. High-resolution melting analysis was used to determine the CYP1A2 polymorphisms. No significant association in prostate cancer risk was seen for CYP1A2 rs2472299 and rs11072508. However, a significantly decreased risk of prostate cancer was found for CYP1A2 rs2470890 [odds ratio (OR), 0.67; P=0.02] in the recessive model. After analysis of the associations of clinical status and these three CYP1A2 polymorphisms, the CYP1A2 rs2470890 and rs11072508 polymorphisms showed a positive association with a higher Gleason score (rs2470890 OR, 1.36, P=0.04 in the allelic model; rs11072508 OR, 1.37, P=0.04 in the allelic model and OR, 1.60, P=0.03 in the dominant model). All three polymorphisms showed a significant positive association with pathological T stage in the additive, allelic and dominant genetic models (P<0.05). Haplotype analysis revealed that the most common haplotypes 'GTT' and 'ACC' were significantly associated with pathological T stages 3 and 4 (OR, 0.62; P=0.02 and OR, 1.54; P=0.03, respectively). A significant association was found between the 'GTT' haplotype and the Gleason score (OR, 0.71; P=0.03). In conclusion, these CYP1A2 polymorphisms and haplotypes have the potential to predict prostate cancer disease progression.
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BACKGROUND/AIM: Our aim was to investigate possible influences of genetic variants in genes involved in the G1/S transition [cyclin-dependent kinase-2 (CDK2), cyclin E1 (CCNE1) and cyclin-dependent kinase inhibitor 1B (p27KIP1)] on the expression/activity of their corresponding proteins and to assess the functional impact of these variants on the risk of prostate cancer. MATERIALS AND METHODS: We genotyped 530 cases and 562 healthy controls for two relevant single nucleotide polymorphisms (CDK2 rs2069408 and CCNE1 rs997669) by TaqMan genotyping assay. p27KIP1 rs2066827 polymorphisms were studied by polymerase chain reaction-restriction fragment length polymorphism assay. In addition, the expression of CDK2, CCNE1 and p27KIP1 was evaluated by quantitative real-time-polymerase chain reaction and western blotting in 44 prostate cancer tissues and 31 benign prostatic hyperplasia tissues. RESULTS: No association was found between CDK2 rs2069408, CCNE1 rs997669 or p27KIP1 rs2066827 polymorphisms and an increased risk of prostate cancer development. Higher CDK2 expression was more prevalent in those with rs2069408 GG genotype than in AA carriers (p>0.05). We also noted reduced p27KIP1 protein expression in those with the p27KIP1 G109 allele. No difference was observed for CCNE1 expression in relation to the risky genotype (CC). A significant association was detected between CCNE1 mRNA overexpression and development of higher-grade carcinomas (Gleason score >7, p<0.05). CONCLUSION: Polymorphisms CDK2 rs2069408, CCNE1 rs997669 and p27KIP1 rs2066827 have no significant impact on prostate cancer risk nor on the gene and protein expression of CDK2, CCNE1 and p27KIP1, although high CCNE1 expression was significantly associated with a higher tumour grade in patients with prostate cancer.
Assuntos
Proteínas de Ciclo Celular , Ciclina E , Quinase 2 Dependente de Ciclina , Inibidor de Quinase Dependente de Ciclina p27 , Proteínas Oncogênicas , Neoplasias da Próstata , Proteínas de Ciclo Celular/genética , Ciclina E/genética , Quinase 2 Dependente de Ciclina/genética , Inibidor de Quinase Dependente de Ciclina p27/genética , Variação Genética , Humanos , Masculino , Proteínas Oncogênicas/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologiaRESUMO
Genetic analyses of STR markers provide data for several important applications, including criminal caseworks, kinship analyses and population studies. In this study, we describe the parameters of nine STR markers (D2S1360, D3S1744, D4S2366, D5S2500, D6S474, D7S1517, D8S1132, D10S2325, D21S2055) in Slovak population and compare them with several European and worldwide populations. Since these markers are not commonly used in forensic practice, our data might provide subsidiary discriminatory power in the most demanding criminal examinations, where additional markers need to be analyzed. Moreover, we performed the MDS analysis and constructed a phylogenetic tree representing genetic relationships between several European populations based on Nei's DA distance. We show that the analysis of just 9 markers is sufficient for reliable clustering of different European populations and their separation from the populations from other geographical areas. Taken together, our data provide a reliable dataset characterizing the Slovak population, which might serve as a basis for criminal, population and kinship studies.
Assuntos
Impressões Digitais de DNA , Genética Populacional , China , Frequência do Gene , Humanos , Repetições de Microssatélites/genética , Filogenia , EslováquiaRESUMO
BACKGROUND/AIM: The aim of this study was to evaluate the relationship between MDM2 T309G polymorphism and prostate cancer risk in the Slovak population and the association of this polymorphism with MDM2 expression and clinicopathological features. MATERIALS AND METHODS: The MDM2 T309G polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 506 prostate cancer patients and 592 controls. Quantitative real-time (RT)-PCR and western blot analysis were applied to examine MDM2 expression in 47 prostate cancer tissues and 43 benign prostatic hyperplasia (BPH) tissues. RESULTS: A decreased risk of prostate cancer in men carrying the GG genotype in comparison with the TT genotype was found. A decrease in the relative MDM2 mRNA and protein levels was found in prostate cancer tissues among patients with the MDM2 GG genotype. CONCLUSION: There is a potentially protective effect of the MDM2 GG genotype on the risk of prostate cancer in the Slovak male population.
Assuntos
Regulação Neoplásica da Expressão Gênica , Estudos de Associação Genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Neoplasias da Próstata/genética , Proteínas Proto-Oncogênicas c-mdm2/genética , Idoso , Estudos de Casos e Controles , Frequência do Gene , Humanos , Masculino , Neoplasias da Próstata/patologia , Fatores de Risco , EslováquiaRESUMO
AIM: To estimate and compare the 2016 numbers and proportions of deaths from selected types of malignant neoplasms attributable to high body mass index (BMI) from 2008 in the Czech and Slovak populations. Material and methods: The estimated impact of overweight and obesity on the risk of malignant neoplasms in the Czech and Slovak populations was calculated using the population attributable fraction (PAF). RESULTS: It is estimated that 2 120 deaths in the Czech Republic and 1 073 deaths in the Slovak Republic in 2016 could be attributable to high BMI. The highest PAF was observed for oesophagal adenocarcinoma in all age categories regardless of sex and country. CONCLUSIONS: It can be stated that high BMI has an impact on selected types of malignant neoplasms. A generally higher PAF was observed for females. At the same time, females showed an increasing PAF with increasing age. This can be explained by weight increase with age in the ageing female population.
Assuntos
Neoplasias , Obesidade , Sobrepeso , Fatores Etários , República Tcheca/epidemiologia , Feminino , Humanos , Masculino , Neoplasias/complicações , Neoplasias/epidemiologia , Obesidade/complicações , Sobrepeso/complicações , Fatores de Risco , Eslováquia/epidemiologiaRESUMO
BACKGROUND: Major depressive disorder (MDD) is a main public health concern worldwide. Despite extensive investigations, the exact mechanisms responsible for MDD have not been identified. Epidermal growth factor (EGF) and insulin growth factor binding protein-3 (IGFBP-3) are involved in brain function. Tumour suppressor protein p53 is widely involved in neuronal death in response to different forms of acute insults and neurological disorders. The present study focuses on the possible associations of the single-nucleotide polymorphisms (SNP) of EGF A61G (rs4444903), IGFBP-3 C32G (rs2854746) and TP53 G72C (rs1042522) genes with MDD risk in the Slovak population. METHODS: The present case-control association study was carried out in 111 confirmed MDD patients and 207 healthy subjects. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism methods. RESULTS: Logistic regression analysis showed no association between SNPs of selected genes and MDD risk in the Slovak population. However, the stratification of individuals by gender revealed that males carrying IGFBP-3 G alleles (G32G or GG) had marginally increased risk for developing MDD as compared to CC homozygous males (p=0.09). In women, inverse association was observed between SNP rs1042522 and MDD risk (p=0.04 for recessive model). CONCLUSION: Our results suggest the protective effect of minor allele 72C of TP53 gene towards MDD. The disruption of mechanisms involved in cell survival and death regulation may be involved in pathophysiology of MDD.
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Transtorno Depressivo Maior/genética , Fator de Crescimento Epidérmico/genética , Genes p53/genética , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Eslováquia/epidemiologiaRESUMO
Cell cycle deregulation is common in human cancer. Alterations of the tumor-suppressor gene p53 and its downstream effector p21 have been indicated in the development of numerous human malignancies. Therefore, we hypothesize that the p53 codon 72 polymorphism, either on its own or in combination with p21 (C98A and C70T) polymorphisms, modifies the risk of prostate cancer within the Slovak population, and no previous studies have investigated these gene-gene interactions in the pathogenesis of prostate cancer in the Slovak population. Polymerase chain reaction-restriction fragment length polymorphism was used to determine the p53 and p21 genotypes in subjects comprising 300 prostate cancer patients and 446 healthy individuals. These 3 polymorphisms individually did not correlate with the prostate cancer risk. Conversely, the interaction between the p53 and p21 polymorphisms significantly decreased the risk of prostate cancer, with the odds ratio (OR) being 0.49 [95% confidence interval (CI), 0.27-0.86; P<0.05] for subjects carrying the p53 codon 72 arginine (Arg)/proline (Pro)+Pro/Pro and p21 C98A CA genotypes compared to the combined reference genotypes p53 codon 72 Arg/Arg and p21 C98A CC. Neither the p53 genotypes nor the p21 genotypes showed statistically significant differences in Gleason score or serum prostate-specific antigen levels (P>0.05). A decreased risk of prostate cancer association with the p21 C98A CA genotype (OR=0.58; 95% CI, 0.36-0.93; P<0.05) in non-smokers compared to the non-smokers with the p21 C98A CC genotype was observed. Smokers carrying the p53 codon 72 Pro/Pro genotype were not at any significant risk of prostate cancer (OR=2.97; 95% CI, 0.51-17.15) compared to the non-smokers with the Arg/Arg genotype. Taken together, to the best of our knowledge this is the first study to show that a combination of the variant genotypes of p53 codon 72 and p21 C98A may modify the prostate cancer risk within the Slovak population.
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OBJECTIVE: Warfarin represents the most commonly prescribed oral anticoagulants, which functions as an antagonist of vitamin K, an essential factor of blood coagulation cascade. Warfarin has a narrow therapeutic index. An insufficient dose can cause failure of antithrombotic effect, and an overdose increases a risk of bleeding. It is known that variability in two genes (CYP2C9 and VKORC1) has a significant effect on individual response to warfarin dose. These polymorphisms influence more than one-third of known warfarin dose effect. Pharmacogenetics of warfarin is less affected by polymorphisms in the other genes such as CYP4F2, CYP2C19, and GGCX. MATERIAL AND METHODS: The frequency of selected single nucleotide polymorphisms including CYP2C9*2 (430C > T), CYP2C9*3 (1075A > C), VKORC1*2 (-1639G > A/1173C > T), VKORC1*3 (3730G > A), GGCX (12970C > G, 8016G > A), CYP2C19*2 (681G > A), and CYP4F2*3 (1297G > A) was tested in a control group consisting of 112 randomly selected individuals by allele-specific real-time PCR, restriction fragment length polymorphism, and bidirectional PCR allele-specific amplification. RESULTS AND DISCUSSION: The current results were statistically evaluated and compared with other populations. The presented results in Slovak population which is in Hardy-Weinberg equilibrium were compared with the prevalence in different countries. The incidence of selected polymorphisms in Slovak population correlates with Caucasians.
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Anticoagulantes/farmacologia , Farmacogenética , Polimorfismo de Nucleotídeo Único , Varfarina/farmacologia , População Branca/genética , Adulto , Alelos , Citocromo P-450 CYP2C9/genética , Sistema Enzimático do Citocromo P-450/genética , Feminino , Frequência do Gene , Genética Populacional , Genótipo , Humanos , Masculino , Eslováquia , Vitamina K Epóxido Redutases/genéticaRESUMO
The foot measurements are important in forensic field as they can be used as body height predictors for an individual. The morphology of human feet shows the variations and therefore the aim of this study was to find the relation between stature and foot measurements and to generate population-specific equations. We measured the stature and bilateral foot measurements of 71 volunteers ranging in age between 18 and 27 years using standard measurements technique. The results revealed nonsignificant bilateral differences in all sex groups (p < 0.05). Sex differences were found to be significant in all foot measurements (p < 0.001). The highest significant and positive correlation coefficients with stature were observed for foot length in males (r = 0.759), in females (r = 0.722), and in the sex-mixed group (r = 0.865). According to the nonsignificant sex effects on the relation between stature and foot dimensions, the regression equations were computed only for the pooled mixed-sex group. Our study provides equations that can help to estimate stature from foot measurements among Slovaks.