The role of base excision repair in pathogenesis of breast cancer in the Polish population.

Breast cancer (BC) is leading type of cancer among group of women, which determines almost 23% of invasive cancers. It has been reported repeatedly that the level of oxidative stress is higher for BC in comparison to cancer-free woman. The goal of the present study was to evaluate the role of base excision repair (BER) pathway in the development of BC. One-hundred seventy-one women with confirmed BC and 222 healthy controls were enrolled in presented study. The level of oxidative DNA damage and the kinetic of their repair were analyzed by the modified alkaline comet assay. The efficiency of BER pathway was evaluated by BER assay. The presence of the 326Cys/Cys genotype and 326Cys allele of OGG1 gene and the 324His/His of MUTYH gene are associated with increased risk of BC development. Moreover, correlation between clinical parameter with selected genes has shown increased risk of BC progression. The survival analysis has shown a significant lower DFS for individuals with the 762Ala/Ala genotype compared to 762Val/Vla carriers and the 762Val/Ala genotype in relation to concomitant chemotherapy and radiotherapy. In subgroup of patients with alone chemotherapy and alone radiotherapy, the 762Val/Val genotype was significantly associated with lower overall survival. Furthermore, we also elevated the level of basal and oxidative DNA damage in a group of patients with BC in relation to healthy controls. We also observed the difference in effectiveness of DNA damage repair. The results of present studies suggested the important role of BER pathway in BC development. © 2015 Wiley Periodicals, Inc.

The analysis of single nucleotide polymorphisms of the DGCR8 and XPO5 genes, and their association with the incidence of primary open angle glaucoma. / Analiza polimorfizmów pojedynczych nukleotydów genów DGCR8 i XPO5 oraz ich zwiazek z wystepowaniem jaskry pierwotnej otwartego kata.

Purpose: To analyse the single nucleotide polymorphisms of DGCR8 and XPO5 genes, involved in miRNA processing pathway, in relation to the incidence of primary open-angle glaucoma. Material and methods: Blood samples as the biological material used for the experiment were voluntarily donated by patients with known primary open-angle glaucoma and age-matched healthy controls. The two control groups ­ rs3757 DGCR8 and rs11077 XPO5 ­ consisted of 135 and 140 volunteers, respectively. The two study groups ­ rs3757 DGCR8 and rs11077 XPO5 ­ consisted of 137 and 138 subjects, respectively. The polymorphic variant frequencies of rs3757 and rs1107 were determined using DNA isolated from the peripheral blood lymphocytes in TaqMan® SNP Genotyping Assays. Results: The statistical analysis revealed that the genotype AG of DGCR8 rs3757 occurred more frequently in healthy individuals (P = 0.001), while homozygote GG was present mostly in people affected by primary open-angle glaucoma (P = 0.003). No association between the risk of primary open angle glaucoma and AC/CC genotypes of XPO5 was found. Conclusions: Many reports suggest the association between the miRNA alteration and the pathogenesis of glaucoma. The single nucleotide polymorphisms in DGCR8 and XPO5 genes, involved in microRNA biogenesis, may be the key factor in this process. Our experiment showed that genotype AG in rs3757 DGCR8 exhibits protective effect, decreasing the risk of primary open angle glaucoma, while the homozygote GG is probably associated with increased risk of glaucoma. The analysis of polymorphic variants of the genes involved in miRNA biogenesis could enable identification of glaucoma high-risk groups.

The role of polymorphisms of genes CXCL12/CXCR4 and MIF in the risk development IBD the Polish population.

Inflammatory bowel disease (IBD) are characterized recurrent inflammation of gastrointestinal tract. The etiology and pathogenesis this disease is currently unclear, but it has become evident that immune and genetic factors are involved in this process. The aim of this study was to determine whether gene polymorphisms: MIF-173 G/C; CXCL12-801 G/A and CXCR4 C/T exon 2 position of rs2228014 is associated with susceptibility to IBD. A total of 286 patients were examined with IBD, including 152 patients with ulcerative colitis and 134 with Crohn's disease (CD) and 220 healthy subjects were recruited from the Polish population. Genotyping for polymorphisms in CXCL12/CXCR4 and MIF was performed by RFLP-PCR. Statistical significance was found for polymorphisms CXCR4, a receptor gene for CXCL12 genotypes and alleles in CD and for genotype C/T and T allele in ulcerative colitis with respect to control. This confirms the effect of CXCL12 gene. The interplay between CXCL12 and its receptor CXCR4 affects homeostasis and inflammation in the intestinal mucosa. Three-gene analysis in CD confirmed the association of genotype GGGGCT. Statistical analysis of clinical data of patients with ulcerative colitis showed significant differences in the distribution of genotype C/T and T allele for CXCR4 in the left-side colitis. Having CXCR4/CXCL12 chemokine axis polymorphisms may predispose to the development of IBD. Activation can also be their defensive reaction to the long-lasting inflammation.

Alterations in expression profile of iron-related genes in colorectal cancer.

Iron can play a role in colorectal cancer (CRC) development. The expression of genes involved in iron metabolism and its regulation in CRC has not been investigated well. Also the correlation between the level of iron-related genes expression and cancer progression is not known. In this study we collected paired samples of primary adenocarcinoma and adjacent normal mucosa from 73 patients. We assessed the mRNA or miRNA levels of 21 genes and verify their association with clinicopathological characteristics of CRC patients. Our experiments revealed, that the level of divalent metal transporter 1 transcript is well correlated with mRNA levels of iron regulatory proteins (IRPs) in tumor specimens. We have shown, that IRP2 can also be engaged in the mRNA stabilization of other iron transporter-transferrin receptor 1 (TfR1) in early stage of disease, however, in more advanced stages of CRC, mRNA level of TfR1 is related to miR-31 level. For the first time we have shown, that ferroportin concentration is significantly associated with miR-194 level, causing the reduction of this transporter amount in tumor tissues of patients with more advanced stages of CRC. We have also shown the alterations in expressing profile of miR-31, miR-133a, miR-141, miR-145, miR-149, miR-182 and miR-194, which were observed even in the early stage of disease, and identified a set of genes, which take place in correct assigning of patients in dependence of CRC stage. These iron-related genes could become potential diagnostic or prognostic indicators for patients with CRC.

Single nucleotide polymorphisms of NR3C1 gene and recurrent depressive disorder in population of Poland.

Depressive disorder is a disease characterized by disturbances in the hypothalamo-pituitary-adrenal axis. Abnormalities include the increased level of glucocorticoids (GC) and changes in sensitivity to these hormones. The changes are related to glucocorticoid receptors gene (NR3C1) variants. The NR3C1 gene is suggested to be a candidate gene affecting depressive disorder risk and management. The aim of this study was to investigate polymorphisms within the NR3C1 gene and their role in the susceptibility to recurrent depressive disorder (rDD). 181 depressive patients and 149 healthy ethnically matched controls were included in the study. Single nucleotide polymorphisms were assessed using polymerase chain reaction/restriction fragment length polymorphism method. Statistical significance between rDD patients and controls was observed for the allele and genotype frequencies at three loci: BclI, N363S, and ER22/23EK. The presence of C allele, CC, and GC genotype of BclI polymorphism, G allele and GA genotype for N363S and ER22/23EK variants respectively were associated with increased rDD risk. Two haplotypes indicated higher susceptibility for rDD, while haplotype GAG played a protective role with OR(dis) 0.29 [95 % confidence interval (CI) = 0.13-0.64]. Data generated from this study support the earlier results that genetic variants of the NR3C1 gene are associated with rDD and suggest further consideration on the possible involvement of these variants in etiology of the disease.

Association of the 399Arg/Gln XRCC1, the 194 Arg/Trp XRCC1, the 326Ser/Cys OGG1, and the 324Gln/His MUTYH gene polymorphisms with clinical parameters and the risk for development of primary open-angle glaucoma.

BACKGROUND: Numerous data have shown that progressive loss of human trabecular meshwork (TM) cells may be connected with oxidative stress. This hypothesis may suggest an association of base excision repair with the risk of primary open angle glaucoma development. PURPOSE: The aim of this study was to evaluate the role of the 399Arg/Gln XRCC1, the 194 Arg/Trp XRCC1, the 326SerCys OGG1, and the 324Gln/His MUTYH gene polymorphisms with clinical parameters and the risk for development of POAG. METHODS: Our research included 170 patients with POAG and 193 healthy controls. Gene polymorphisms were investigated by PCR-RFLP. The Heidelberg Retinal Tomography (HRT) clinical parameters were also analyzed. RESULTS: The 399Arg/Gln genotype of the XRCC1 gene was associated with an increased risk for POAG (OR 2.50; 95% CI, 1.54-4.07, P=0.0002). The 399Gln/Gln XRCC1 genotype may increase the risk for POAG progression according to clinical parameters such as cup/disk ratio (c/d) (OR 1.93; 95% CI, 1-3.73, P=0.04) and Rim area (RA factor) (OR 3.88; 95% CI, 1.01-14.82, P=0.04). Moreover, an association was found of retinal nerve-fiber layer (RNFL factor) with the 399Arg/Gln XRCC1 genotype distribution and POAG progression (OR 2.46; 95% CI, 1.06-5.68, P=0.03). In contrast, analysis of the 324Gln/His MUTYH gene polymorphism distribution in the patient group according to RA factor showed that it may reduce the progression of POAG (OR 0.14; 95% CI, 0.02-0.89, P=0.05). Our current study demonstrates an association between the 326Ser/Cys OGG1 gene polymorphism and the 326Cys allele of the OGG1 gene, and progression of POAG. In addition, the presence of the 326His allele of the MUTYH gene may increase the risk for POAG progression, according to the VF parameter (OR 2.57; 95% CI, 1.47-4.57, P=0.0001). CONCLUSION: We suggest that the 399Arg/Gln genotype and the 399Gln allele of the XRCC1 gene may be risk factors for POAG development. Moreover, we postulate that the 399 Arg/Gln XRCC1, the 326 Ser/Cys OGG1 and the 324 Gln/His MUTYH genes polymorphisms may be associated with progression of POAG.

Association of Thr241Met polymorphism of XRCC3 gene with risk of colorectal cancer in the Polish population.

DNA double strand breaks (DSBs) are the most dangerous lesions which can lead to carcinogenesis. Homologous recombination (HR) is an important pathway responsible for maintaining genome integrity through repair of DSBs. Single nucleotide polymorphism (SNP) is an essential source of genetic variation whose presence in genes involved in HR may have a crucial role in modulation of DNA repair capacity. This case-control study was designed to evaluate the influence of XRCC3 gene Thr241Met polymorphism on CRC risk and progression among Polish population. Genotyping was performed by RFLP-PCR (restriction length fragment polymorphism). The subject of our study was consist of 194 patients with CRC and 204 cancer-free individuals who were age and sex-matched as a control group. Obtained genotype distributions in controls as well as patients fit to the Hardy-Weinberg expectations. Odd ratio analysis indicates diminished risk for heterozygous model and Met allele. Comparison of patients with noninvasive and advanced stage of CRC did not imply any statistical significance. Our results suggest that Thr241Met XRCC3 gene polymorphism might be regarded as CRC potential molecular marker. Nevertheless, that hypothesis needs to be confirmed by subsequent studies.

Altered Tryptophan Metabolism on the Kynurenine Pathway in Depressive Patients with Small Intestinal Bacterial Overgrowth.

The causes of depression are diverse and are still not fully understood. Recently, an increasing role is attributed to nutritional and inflammatory factors. The aim of this study was to evaluate selected metabolites of the tryptophan kynurenine pathway in depressive patients with small intestinal bacterial overgrowth (SIBO). The study involved 40 healthy people (controls) and 40 patients with predominant small intestinal bacterial overgrowth (SIBO-D). The lactulose hydrogen breath test (LHBT) was performed to diagnose SIBO. The severity of symptoms was assessed using the Gastrointestinal Symptom Rating Scale (GSRS-IBS) and the Hamilton Depression Rating Scale (HAM-D). The concentration of tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QA) in urine was determined using an LC-MS/MS method, before and after cyclic treatment with an antibiotic drug, rifaximin, for three months. The number of intraepithelial lymphocytes (IELs) in the duodenum and small intestinal mucosa, fecal calprotectin (FC) and serum level of C-reactive protein (CRP) were also determined. In patients with SIBO, a higher level of KYN and QA were found as compared to the control group. These two groups also differed in KYN/TRP (higher in SIBO) and KYNA/KYN ratios (lower in SIBO). A positive correlation was found between HAM-D and the number of IELs and the level of FC. Treatment with rifaximin improves the kynurenic pathway, as well as abdominal and mental complaints. Therefore, small intestinal bacterial overgrowth can be a cause of abdominal symptoms, but also mental disorders.

The Role of the ER-Induced UPR Pathway and the Efficacy of Its Inhibitors and Inducers in the Inhibition of Tumor Progression.

Cancer is the second most frequent cause of death worldwide. It is considered to be one of the most dangerous diseases, and there is still no effective treatment for many types of cancer. Since cancerous cells have a high proliferation rate, it is pivotal for their proper functioning to have the well-functioning protein machinery. Correct protein processing and folding are crucial to maintain tumor homeostasis. Endoplasmic reticulum (ER) stress is one of the leading factors that cause disturbances in these processes. It is induced by impaired function of the ER and accumulation of unfolded proteins. Induction of ER stress affects many molecular pathways that cause the unfolded protein response (UPR). This is the way in which cells can adapt to the new conditions, but when ER stress cannot be resolved, the UPR induces cell death. The molecular mechanisms of this double-edged sword process are involved in the transition of the UPR either in a cell protection mechanism or in apoptosis. However, this process remains poorly understood but seems to be crucial in the treatment of many diseases that are related to ER stress. Hence, understanding the ER stress response, especially in the aspect of pathological consequences of UPR, has the potential to allow us to develop novel therapies and new diagnostic and prognostic markers for cancer.

The 116G > A MSH6 and IVS1-1121C > T PMS2 Genes Polymorphisms Modulate the Risk of the Sporadic Colorectal Cancer Development in Polish Population.

Colorectal cancer (CRC) is one of the most common cancers worldwide. DNA mismatch repair (MMR) is an evolutionarily conserved process that corrects mismatches generated during DNA replication. MMR defects were found to be associated with hereditary non-polyposis colorectal cancer (HNPCC) and a subset of sporadic colon cancers. The inheritance of common variations in MMR genes may influences individual susceptibility to the development of colorectal cancer. The purpose of the study was to evaluate the association between gene polymorphisms Glu39Gly (c.116G > A) of MSH6 gene and IVS1-1121C > T of PMS2 gene and sporadic colorectal cancer risk, in a case-control study comprising 200 patients and 200 controls origination from polish population. DNA was isolated from peripheral blood lymphocytes of enrolled patients, and gene polymorphisms were analysed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) for MSH6 and TaqMan for PMS2. G/A variant of Glu39Gly (c.116G > A) genotype was associated with an increased risk of colorectal cancer (OR 1,65 95%CI:1,01-2,69 p = 0.44). Presence of A allele was also significantly higher in patient with CRC (OR 1,57 95% CI: 1,04-2,38 p = 0.032). Prevalence of this genotype was also markedly higher in females and patients above 60 years in CRC group (OR 2.25 95%CI: 1.22-4.14 p = 0.0098 and OR 2.74 95% CI: 1.27-5.93 p = 0.0097 respectively). None of such correlations was observed for genotype variants of IVS1-1121C > T PMS2. In conclusion, our data suggests thatMSH6 Glu39Gly polymorphism is associated with the risk of developing sporadic colorectal cancer in polish population. Linkage to the female gender, onset above 60 years old and further increase of risk when combined with wild-type allele of PMS2 IVS1-1121C > T polymorphism indicates defective mismatch repair system.

Analysis of the polymorphic variants of RAN and GEMIN3 genes and risk of Primary Open-Angle Glaucoma in the Polish population.

BACKGROUND: Glaucoma is considered as a neurodegenerative disorder in which the optic nerve damage leads to irreversible blindness. Many scientific findings indicate miRNA implication in the neurodegeneration process. In this study, we aimed to evaluate the polymorphic variants of miRNA processing genes, RAN (rs14035) and GEMIN3 (rs197388), and their association with a risk of primary open-angle glaucoma (POAG) in relation to selected clinical parameters. MATERIALS AND METHODS: The study included 246 POAG patients and 188 controls. The selected gene polymorphisms were analyzed by TaqMan SNP Genotyping Assay using DNA extracted from blood samples. RESULTS: The obtained results indicated that the AA genotype of rs197388 as well as the A allele in the same gene may be associated with an elevated risk of POAG development (P = 0.021, P = 0.017 respectively). The correlation between the data and clinical parameters has shown that the A allele of rs197388 in relation to retinal nerve fiber layer(RNFL) could be responsible for an increased risk of glaucoma occurrence (P = 0.028), while the AT genotype could be associated with a decreased risk of POAG according to the mean deviation parameter (P = 0.023). CONCLUSION: Our data has shown that GEMIN3 gene (rs197388) polymorphisms might be associated with a risk of POAG development in the Polish population. This is the first report evaluating the polymorphic variants of miRNA processing genes, RAN and GEMIN3, with a changed risk of glaucoma.

Nucleotide Excision Repair Capacity and XPC and XPD Gene Polymorphism Modulate Colorectal Cancer Risk.

BACKGROUND: Colorectal cancer (CRC) is leading malignant tumors to occur mainly in industrialized countries, where it exhibits one of the highest mortality rates. Up to 80% of all CRCs characterize a chromosomal instability (CIN) phenotype. The main challenge faced by scientist is to reveal the mechanism of CIN development. An often proposed model is defects in DNA repair in terms of efficiency and genetic variations that modulate the response to stimuli from the environment. The objectives of this research were to determine whether nucleotide excision repair (NER) might affect CRC risk. MATERIALS AND METHODS: The first part of the study concerns NER efficiency. In the second part we selected 2 common single nucleotide polymorphisms within genes involved in NER (Xeroderma pigmentosum group C (XPC) Lys939Gln, Xeroderma pigmentosum group D (XPD) Lys751Gln) to determine the relation between them and CRC risk. The restriction fragment length polymorphism-polymerase chain reaction method was used for genotyping of 221 CRC patients vs. 270 cancer-free individuals. The isotopic labeling in vitro assay was used to evaluate NER capacity in lymphocytes and tissue protein extracts. RESULTS: We observed a significantly decreased level of NER capacity (P = .025) in lymphocytes delivered from CRC patients compared with healthy ones. Polymorphism screening points to higher CRC risk for the Gln939Gln genotype (P = .02) and Gln allele (P = .002) of the XPC gene. CONCLUSION: Taken together, our findings suggest a potential role for NER in CRC.

Polymorphism of Gly39Glu (c.116G>A) hMSH6 is associated with sporadic colorectal cancer development in the Polish population: Preliminary results.

BACKGROUND: Colorectal cancer (CRC) remains a major source of cancer-related mortality, accounting for 10% of all cancer-related deaths. DNA mismatch repair mechanism (MMR) responsible for correcting errors generated during DNA replication and its deficiency is associated with both hereditary and sporadic CRC. Single-nucleotide polymorphisms (SNPs) are the most common forms of genetic variation, and it has been shown that the SNPs in MMR genes may modify CRC risk. OBJECTIVES: The aim of the study was to determine the relationship between gene polymorphism Glu39Gly (c.116G>A) of the hMSH6 gene and the modulation of the risk of sporadic colorectal cancer in the Polish population. MATERIAL AND METHODS: A total of 128 patients with resectable colorectal carcinoma as well as 189 sex-, age-, and ethnicity-matched control subjects without cancer history were enrolled in this study. Patients with a family history of CRC or inflammatory bowel diseases were excluded from this study. The DNA was isolated from peripheral blood lymphocytes of enrolled patients, and gene polymorphisms were analyzed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). RESULTS: We observed that the genotype G/A variant of Glu39Gly (c.116G>A) genotype is associated with an increased risk of colorectal cancer (OR 1.65; 95% CI: 1.01-2.69; p = 0.44). The presence of A allele was also significantly higher in patients with CRC (OR 1.57; 95% CI: 1.04-2.38; p = 0.032). When comparing the prevalence of genotypes with clinical staging, genotype G/A and A allele were significantly less frequent in stage III-IV than in I (OR 0.3409; 95% CI: 0.124-0.939; p = 0.0375, and OR 0.4462; 95% CI: 0.201-0.991; p = 0.044, respectively). CONCLUSIONS: These findings suggest that hMSH6 Glu39Gly polymorphism is associated with the risk of developing colorectal cancer in the Polish population, probably due to a defective mismatch repair system. The presence of G/A genotype and A allele is, however, associated with less advanced disease.

Carbon nanotubes functionalized with folic acid attached via biomimetic peptide linker.

AIM: Anchoring folic acid (FA) with a biomimetic peptidic linker resistant to proteolytic degradation to act as a homing device on functionalized carbon nanotubes. MATERIALS & METHODS: Ethylenediamine was attached to oxidized multiwalled carbon nanotubes (MWNTs) using 4-(4,6-dimethoxy-[1,3,5]triazin-2-yl)-4-methylmorpholinium tetrafluoroborate. FA was coupled with 6-aminohexanoic acid and derivatives of ß-alanine, affording four intermediates, which connected to the MWNTs via peptidic linkers of various lengths. RESULTS: Biomimetic nanomaterials were produced with FA as a homing molecule. The structure and properties of the nanomaterials were analyzed, confirming the versatility of the peptides used as linkers. CONCLUSION: Conjugates of FA attached to MWNTs via peptide linkers prepared from ß-alanine residues are resistant to proteolytic degradation. Viability in colon cancer cells and normal colonocytes confirmed their lack of cytotoxicity.

An association of the MCP-1 and CCR2 single nucleotide polymorphisms with colorectal cancer prevalence.

THE AIM OF THE STUDY: We evaluated the connection between the presence of the -2518 A/G MCP-1 as well as 190 G/A CCR2 polymorphic variants and colorectal cancer (CRC) occurrence. MATERIAL AND METHODS: Study group consisted of subjects with different stages of CRC as well as healthy controls. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: W observed an association between the colorectal cancer and the GG genotype of the -2518 A/G MCP-1 single nucleotide polymorphism. No statistically significant correlation was found between CRC and the 190 G/A CCR2 polymorphism. CONCLUSION: The results of this study support the hypothesis that polymorphism in the MCP-1 gene may contribute to the etiology of colorectal cancer.

Polymorphism within the distal RAD51 gene promoter is associated with colorectal cancer in a Polish population.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers in developed countries. Annually, over one million of new cases in the world are recorded. Majority of CRCs occur sporadically with dominant phenotype of chromosomal instability (CIN). Permanent exposure to DNA damaging agents such as ionizing radiation result in DNA double-stranded breaks, which create favorable conditions for chromosomal aberration to arise. Homologous recombination repair (HRR) is the leading process engaged in maintaining of the genome integrity. RAD51 protein was recognized as crucial in HRR. Single nucleotide polymorphisms are the primary source of genetic variation which presence in the RAD51 promoter region can affect on its expression and consequently modulate HR efficiency. OBJECTIVES: The aim of this study was to analyze the distribution of genotypes and allele frequencies of -4791A/T and -4601A/G RAD51 gene polymorphisms, followed by an assessment of their relationship with the risk of CRC. MATERIAL AND METHODS: The study included 115 patients with confirmed CRC. Control group was consisted of 118 cancer-free individuals with a negative family history. The genotypes were identified by PCR-RFLP method. CONCLUSION: This study revealed statistically significant association between appearance of G/A genotype in position -4601 of RAD51 gene and CRC risk.

Neurodegenerative Genes Polymorphisms of the -491A/T APOE, the -877T/C APP and the Risk of Primary Open-angle Glaucoma in the Polish Population.

BACKGROUND: Glaucoma is characterized by optic neuropathy of the retinal ganglion cell. It may be possible that ß-amyloid (Aß) and apolipoprotein E (APOE), the main proteins of the pathogenesis of AD, play a role in glaucoma development. The aim of this study was to evaluate a relationship between the APP and APOE gene polymorphisms and the risk of primary open-angle glaucoma (POAG) occurrence. MATERIALS AND METHODS: The study consisted of 183 patients with POAG and 209 healthy subjects. Genomic DNA was extracted from peripheral blood. Analysis of the gene polymorphisms was performed using PCR-RFLP. RESULTS: We found a statistically significant increase of the -491 T allele frequency (p=0.02; OR=1.48; 95% CI=1.06-2.08) of APOE in POAG compared to healthy controls. There were no differences in the genotype and allele distributions and odds ratios of the APP polymorphism between patients and controls group. We also found an association between APOE polymorphic variant and retinal nerve fiber layer (RNFL). There was a statistically significant difference in the APOE gene A/T genotype frequency in the early POAG stage and middle-advanced POAG stage in comparison to the advanced POAG stage (p=0.04; OR=3.38; 95% CI=1.04-10.97). CONCLUSIONS: The -491 T allele of APOE polymorphism may be associated with a risk of POAG occurrence in the Polish population.

Analysis of the expression and polymorphism of APOE, HSP, BDNF, and GRIN2B genes associated with the neurodegeneration process in the pathogenesis of primary open angle glaucoma.

Glaucoma is characterized by optic neuropathy of the RGC or retinal nerve fiber. The aim of this study was to evaluate a relationship between the neurodegenerative genes' polymorphisms of the APOE (rs449647), BDNF (rs2030324), GRIN2B (rs3764028), and HSP70-1 (rs1043618) and the occurrence risk of POAG and to investigate its effect on allele-specific gene expression. Genomic DNA was extracted from peripheral blood. Analysis of the genes' polymorphisms was performed using PCR-RFLP. The level of mRNA expression was determined by QRT-PCR. We showed a statistically significant association of BDNF and APOE genes' polymorphisms with a risk of POAG occurrence. There was a statistically significant association of the rs2030324 polymorphism with progression of POAG based on cup disc ratio value and rs1043618 polymorphism based on nerve fiber index and rim area. Furthermore, we found that mean HSP70-1 mRNA expression was significantly lower in the case of individuals with the G/G genotype than in the case of minor allele carriers, that is, G/C and C/C. We also found that BDNF and HSP70-1 expression level are associated with the progression of POAG based on rim area value. In conclusion, our results suggest that BDNF, APOE, and HSP70-1 genes might be associated with a risk of POAG occurrence in the Polish population.

Expression of the PLS3 Gene in Circulating Cells in Patients with Colorectal Cancer.

UNLABELLED: Circulating tumor cells (CTC) are cells in circulating blood that have the antigen and gene features of tumor cells of a specific type. Since they can be potentially used in diagnostics and monitoring of treatment of many tumors, they have been attracting attention of researchers worldwide. Plastin-3 (PL S3) is one of such markers of CTC. The aim of the study was to assess expression of PL S3 in CTC in patients with colorectal cancer, to conduct a statistical analysis and to demonstrate a link between expression of PL S3 and progress of the disease, level of CEA and Ca19-9 markers, gender and age of the patients. MATERIAL AND METHODS: A group of 85 patients of the Department of General and Colorectal Surgery of the Medical University in Lódz were enrolled in this study. Circulating tumor cells were isolated from whole blood of patients with colorectal cancer and an analysis of PL S3 gene expression in CTC was conducted. The next step was to conduct a statistical analysis and to demonstrate a link between expression of PL S3 in patients' CTC and progress of the disease, level of CEA and Ca 19-9 markers, gender and age of the patients. RESULTS: PL S3 is a marker which can be potentially used in prediction and monitoring of colorectal cancer. A link between expression of PL S3 in CTC of patients with colorectal cancer and metastasis to lymph nodes has been demonstrated. It may be of key importance how PL S3 could impact the qualification to supplementary cancer treatment in patients with stage II colorectal cancer. A link between expression of PL S3 gene in CTC and gender requires further in-depth studies. It is beyond doubt that PL S3 must be further investigated to determine its role in diagnostics, prediction, treatment and monitoring of treatment of colorectal cancer.

Expression of POSTN, IL-4, and IL-13 in Chronic Rhinosinusitis with Nasal Polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is one of the most frequently encountered chronic nasal diseases with a significant impact on patient quality of life. The aim of our study was therefore to investigate the association between the POSTN, IL-4, and IL-13 gene expression and the nasal polyp development. The objective of this study was to determine differential expression of POSTN, IL-4, and IL-13 genes in the mucosa and polyps of 63 patients with CRSwNP and 23 chronic rhinosinusitis (CRS) without nasal polyps (CRSsNP) when compared with patients with nasal septum deviation (n=18) who were used as controls. The expression level was investigated using reverse transcription-polymerase chain reaction assays in the polyp tissue and the mucosa of paranasal sinus collected while undergoing functional endoscopic sinus surgery. Expression of the mRNAs of all three genes, IL-4, IL-13, and POSTN, was significantly greater in the paired tissues of CRS patients with NPs or without NPs than in control subjects, with highest levels of POSTN and IL-13 seen in CRSwNP. An increased level of POSTN, IL-4, and IL-13 gene expression may be related to the development of chronic rhinosinusitis with nasal polyps, but polyp formation seemed to be associated especially with POSTN and IL-13 expression.