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Wioletta Rozpędek, Alicja Nowak, Dariusz Pytel, Dawid Lewko, J. Alan Diehl and Ireneusz Majsterek

Abstract

Alzheimer’s disease (AD) is a highly complex, progressive, age-related neurodegenerative human disease entity. The genetic basis of AD is strictly connected with occurrence of mutations in Amyloid Precursor (APP) gene on chromosome 21. Molecular mechanism that leads to AD development still remains unclear. Recent data reported that it is closely correlated with Endoplasmic Reticulum (ER) stress conditions, which subsequently activate Unfolded Protein Response (UPR) signaling pathways, via the induction of protein kinase RNA-like endoplasmic reticulum kinase (PERK), as a self-protective, adaptive response to adverse stress conditions. That results in the attenuation of global protein synthesis and, on the contrary, selective translation of Activating Transcriptor Factor 4 (ATF4) and secretase β. Interestingly, under prolonged, severe ER stress UPR may switch its signal into apoptotic cell death. That ensues by ATF4-CHOP-mediated activation of a range of pro-apoptotic genes and, on the other hand, downregulation of the expression of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) genes. Current investigations suggest that inhibitions of PERK activity may contribute to the attenuation of the deposition of toxic senile plaques in the brain tissue and, as a result, prevent degeneration of neurons and decline in cognitive abilities.

Open access

Jacek Kabziński, Ireneusz Majsterek, Adam Dziki and Michał Mik

Abstract

Participation of DNA repair systems in the pathogenesis of cancer has been a suspected phenomenon for a long time. Decreased efficiency in DNA repair translates to their ability to fix and consequently leads to mutations and the process of carcinogenesis. Linking individual polymorphisms of DNA repair systems with an increased risk of colorectal cancer will allow the classification of patients to high-risk groups and their placement under preventive program.

The aim of the study was to determine the effect of XPF gene polymorphism Ser835Ser on increasing the risk of colorectal cancer in the Polish population.

Material and methods. as the material blood collected from 146 patients diagnosed with colon cancer was used. The control group consisted of 149 healthy subjects. Genotyping was performed by Taq- Man method.

Results. The results indicate that genotype TCC/TCT is associated with an decreased risk of colorectal cancer (OR 0.574; CI 95% 0.335-0.984; p=0.043).

Conclusions. Based on these results, we conclude that the XPF gene polymorphism Ser835Ser may be associated with a decreased risk of colorectal cancer

Open access

Bartosz Mucha, Karolina Przybyłowska-Sygut, Łukasz Dziki, Adam Dziki, Andrzej Sygut and Ireneusz Majsterek

Lack of Association Between the 135G/C Rad51 Gene Polymorphism and the Risk of Colorectal Cancer Among Polish Population

One of the major causes of carcinogenesis is loss of genome stability. RAD51 in process of homologous recombination (HR) played crucial role in maintenance integrity of genome through initiate of DNA double strand breaks repair. Presence of single nucleotide polymorphism (SNP) in RAD51 gene could change the capacity of DNA repair and altered the response to damaging agents. Research on potential impact of genetic variability on development and progression CRC may contribute to setting new genetic markers or/and determined individual susceptibility to CRC.

The aim of the study. This study was designed to evaluate the effect of 135 G/C (rs1801320) RAD51 polymorphism located in the 5' untraslated region on the risk and progression of CRC.

Material and methods. The subjects consisted of histologically confirmed colorectal cancer (n = 200) and controls (n = 200) with lack of previous history of cancer. The distribution of genotypes was determined by restriction fragment length polymorphism PCR (RFLP - PCR). Statistical analysis was based on multivariate regression model.

Results and conclusion. Our study reveal no significance association of 135 G/C RAD51 polymorphism with occurrence and progression of colorectal cancer.

Open access

Katarzyna Malinowska, Michał Mik, Łukasz Dziki, Adam Dziki and Ireneusz Majsterek

Abstract

Cancers are among the most feared diseases of modern civilization. In Poland, colorectal cancer is one of the tumors with the worst prognosis. The ability to cure is primarily dependent on the stage of the disease at the time of diagnosis.

The aim of the study was evaluate antioxidant response in patients with colorectal carcinoma.

Material and methods. Twenty patients (14 men and 6 women) aged 61.9± 11.1 years with colorectal cancer were included in the study. Twenty healthy subjects (4 men and 16 women) aged 64 ± 15.3 years formed the control group. The erythrocyte activities of antioxidant enzymes, superoxide dismutase (SOD), and glutathione peroxidase (GPx),

Results. A significant increase of GPx, and SOD (p < 0.05) were seen in patients compared to healthy controls.

Conclusion. The results indicate that the tested antioxidant enzyme activity of glutathione peroxidase and superoxide dismutase is increased in patients diagnosed with colorectal cancer compared to the control group.

Open access

Anna Walczak, Karolina Przybyłowska, Radzisław Trzciński, Andrzej Sygut, Łukasz Dziki, Adam Dziki and Ireneusz Majsterek

Association of -1112 C/T Promoter Region Polymorphism of the Interleukin 13 Gene with Occurrence of Colorectal Cancer

Colorectal carcinoma is one of the leading causes of death from cancer amongst adults. Considering its molecular background, cytokines are the key component of the inflammatory microenvironment of these tumors. Investigations that enable better understanding of colorectal cancer concerning the molecular level, may provide important tools for genetic screening of disease high-risk groups, as well as molecular diagnostics for the non-invasive detection of cancer in its early stages.

The aim of the study was to evaluate the association between colorectal cancer and the -1112 C/T single nucleotide polymorphism (SNP) of the interleukin-13 gene.

Material and methods. The study group comprised 150 cancer patients and 170 healthy subject genotypes from the Polish population. Analysis was performed by PCR-restriction fragment length polymorphism (PCR-RFLP).

Results. We showed that the CT genotype is connected with a higher risk of colon cancer occurrence (OR 2.51; 95% CI 1.57-4.02; p < 0.0001). We also correlated the polymorphic variants of the IL-13 gene with the clinical characteristics of colorectal cancer patients. We observed no association between the investigated polymorphism and colorectal cancer progression, evaluated by tumor stage, as well as lymph node metastasis.

Conclusions. The presented study suggested the possibility of a connection between the IL-13 gene polymorphism (-1112 C/T) and colorectal cancer risk in the Polish population.

Open access

Ewa Langner, Karolina Przybyłowska, Andrzej Sygut, Michał Mik, Łukasz Dziki, Mirosław Dziekiewicz, Ireneusz Majsterek and Adam Dziki

The - 801 G/A Polymorphism of CXCL12 Promoter Gene as Unfavorable Genetic Prognosis factor involved in Colorectal Cancer

CCXL12 also called stromal derived factor-1 (SDF-1), a protein related to angiogenesis and inflammation, has been correlated with the progression of a number of malignancies. Single nucleotide - 801G/A polymorphism of CXCL12 gene has been described and is regarded as a target for cis-acting factor that has the ability to up-regulate CXCL12 expression.

The aim of the study. Based on the suggested role of CXCL12 in the pathogenesis of cancer we examined the association of the gene variant CXCL12-A with colorectal cancer.

Material and methods. We genotyped - 801G/A polymorphism of CXCL12 gene in 164 colorectal patients and 184 age-matched healthy subjects. Genotyping was done with PCR-RFLP.

Results. There were no significant differences in the frequencies of SDF1-3'A allele, between patients and controls. The frequency of CXCL12 G/A and G/A plus A/A genotype was significantly higher in a group of patients with lymph node metastasis compared with those without metastasis.

Conclusions. The CXCL12 gene G/A polymorphism was not related to colorectal cancer risk but is associated with the induction of lymph-node metastasis of colorectal cancer disease in Polish.

Open access

Anna Walczak, Karolina Przybyłowska, Andrzej Sygut, Łukasz Dziki, Cezary Chojnacki, Jan Chojnacki, Adam Dziki and Ireneusz Majsterek

The -2518 A/G MCP-1 Polymorphism as a Risk Factor of Inflammatory Bowel Disease

Inflammatory bowel diseases (IBD) are disorders originated from immune disturbances.

The aim of the study was to evaluate the association between the -2518 A/G MCP-1 polymorphism and the risk of IBD development.

Material and methods. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Study group consisted of 197 subjects with IBD (120 with ulcerative colitis and 77 with Crohn's disease) as well as 210 healthy controls.

Results. The presence of the -2518 G/G MCP-1 genotype in the investigated groups seems to be connected with higher risk of inflammatory bowel disease as well as Crohn's disease only (OR 2.26; 95% CI 1.44-3.54 and OR 2.08; 95% CI 1.21-3.46, respectively).

Conclusions. Our data showed that the -2518 A/G MCP-1 polymorphism might be associated with the IBD occurrence and might be used as predictive factor of these diseases in a Polish population.

Open access

Łukasz Dziki, Karolina Przybyłowska, Ireneusz Majsterek, Radzisław Trzciński, Michał Mik and Andrzej Sygut

A/G Polymorphism of the MMP-7 Gene Promoter Region in Colorectal Cancer

In gastrointestinal malignancies increased expression of matrilysin - MMP-7 - is often observed. Its high level positively correlates with clinical stage of malignancy and is a negative prognostic factor. This suggests a possible relationship between functional polymorphisms of the MMP-7 gene and susceptibility to development of colorectal cancer and an aggressive course of the disease.

The aim of the study was to assess the effects of A/G functional polymorphism at -181 site of the MMP-7 gene promoter region on development and progression of colorectal cancer.

Material and methods. In total, 184 patients treated surgically for colorectal cancer at the Department of General and Colorectal Surgery of the Medical University in Łódź in the years 2006-2009 and a control group of 205 cancer-free individuals with a negative family history for malignancy have been investigated. Polymorphic variants of the MMP-7 gene promoter region have been analysed using the RFLP-PCR method.

Results. A statistically significant difference in distribution of genotypes has been found between the investigated group and the control group, and the OR analysis confirmed a relationship between the A/G [1.67 (1.03-2.72); p= 0.038] and G/G [2.12 (1.34-3.38); p = 0.018] genotypes and an increased risk of colorectal cancer. The risk of lymph node involvement was more than twice higher for the G/G genotype (OR = 2.83 (1.18-6.79); P = 0.017). In addition, the analysis of genotype distribution in patients divided into groups according to the T parameter of the TNM classification revealed a relationship between the G/G genotype and advanced tumour infiltration. No relationship between the investigated A/G polymorphism and the presence of distant metastases has been found.

Conclusions. Obtained results indicate a possible relationship between -181 A/G polymorphism of the MMP-7 gene and malignant transformation of colorectal epithelial cells and progression of colorectal cancer. This suggests applicability of this polymorphism as a predisposing factor for the disease and a prognostic factor, which in the future may be useful in the management algorithm for colorectal cancer.

Open access

Ryszard Kujawski, Michał Mik, Karolina Przybyłowska-Sygut, Ireneusz Majsterek and Adam Dziki

Open access

Karolina Przybyłowska, Jerzy Mrowicki, Andrzej Sygut, Piotr Narbutt, Łukasz Dziki, Adam Dziki and Ireneusz Majsterek

Contribution of the -173 G/C Polymorphism of Macrophage Migration Inhibitory Factor Gene to the Risk of Inflammatory Bowel Diseases

Inflammatory bowel disease (IBD) represents a heterogeneous group of chronic disorders characterized by inflammation of gastrointestinal tract, typically with a relapsing and remitting clinical course of unknown etiology. Presumably, IBD develops with response exogenous environmental factors only in persons with genetic predisposition. This predisposition was suggested to be associated with polymorphism and mutations in genes encoding proinflammatory immune system proteins. Enhanced production of macrophage migration inhibitory factor (MIF) was found in patients with inflammatory bowel disease (IBD) and mice with experimental colitis. These results suggest that MIF plays a critical role in etiology of the colitis.

The aim of the study was determine whether the MIF -173 G/C gene polymorphism is associated with the susceptibility to inflammatory bowel disease (IBD).

Material and methods. A total of 99 IBD patients, including 58 patients with ulcerative colitis (UC) and 41 with Crohn's disease (CD) and 436 healthy controls recruited from the Polish population, were genotyped for MIF polymorphisms. Genotyping of MIF gene polymorphism was performed by a RFLP-PCR.

Results. We found an increased risk of UC for the C allele of the MIF-173 G/C polymorphism. The distribution of the genotypes was not significantly different in the CD group compared with the controls.

Conclusions. We demonstrated that the C allele is associated with an increased risk for development of UC. This suggests that the G/C polymorphism in the MIF gene promoter may be a potential risk factor for UC in Polish population.