Genetic polymorphisms in DNA base excision repair gene XRCC1 and the risk of squamous cell carcinoma of the head and neck

<p>Abstract</p> <p>Background</p> <p>The genes of base excision repair (BER) pathway have been extensively studied in the association with various human cancers. We performed a case-control study to test the association between two common single nucleotide polymorphisms (SNPs) of <it>XRCC1 </it>gene with human head and neck squamous cell carcinoma (HNSCC).</p> <p>Methods</p> <p>The genotype analysis of Arg194Trp and Arg399Gln gene polymorphisms for 92 HNSCC patients and 124 controls of cancer free subjects, in Polish population were performed using the PCR-based restriction fragment length polymorphism (PCR-RFLP) with endonuclease <it>Msp</it>I.</p> <p>Results</p> <p>No altered risk has been found individually for these SNPs, however haplotypes analysis showed high association with head and neck cancer. The highest frequency, according to wild-type of Arg194Arg and Arg399Arg genotypes, was identified for Arg194Trp-Arg399Arg haplotype (OR, 2.96; 95% CI, 1.01–8.80).</p> <p>Conclusion</p> <p>Finally, we identified the combined Arg194Trp-Arg399Arg genotype of base excision repair gene <it>XRCC1 </it>that was associated with HNSCC and may have an impact on identification of a high-risk cancer population.</p

Angiogenesis Markers Quantification in Breast Cancer and Their Correlation with Clinicopathological Prognostic Variables

Tumoural angiogenesis is essential for the growth and spread of breast cancer cells. Therefore the aim of this study was to assess the diagnostic performance of angiogenesis markers in tumours and there reflecting levels in serum of breast cancer patients. Angiogenin, Ang2, fibroblast growth factor basic, intercellular adhesion molecule (ICAM)-1, keratinocyte growth factor (KGF), platelet-derived growth factor-BB, and VEGF-A were measured using a FASTQuant angiogenic growth factor multiplex protein assay. We observed that breast cancer tumours exhibited high levels of PDGF-BB, bFGF and VEGF, and extremely high levels of TIMP-1 and Ang-2, whereas in serum we found significantly higher levels of Ang-2, PDGF-BB, bFGF, ICAM-1 and VEGF in patients with breast cancer compared to the benign breast diseases patients. Moreover, some of these angiogenesis markers evaluated in tumour and serum of breast cancer patients exhibited association with standard clinical parameters, ER status as well as MVD of tumours. Angiogenesis markers play important roles in tumour growth, invasion and metastasis. Our results suggest that analysis of angiogenesis markers in tumour and serum of breast cancer patients using multiplex protein assay can improve diagnosis and prognosis in this diseases

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

Antigen levels of urokinase-type plasminogen activator receptor and its gene polymorphism related to microvessel density in colorectal cancer

We determined the distribution of genotypes and frequencies of alleles of the (CA)n repeat polymorphism in intron 3 of the urokinase plasminogen activator receptor (uPAR) gene, uPAR antigen levels and microvessel density (MVD) in tumour and distant mucosa samples from 52 patients with colorectal cancer. The uPAR level was higher for patients with high MVD comparing to patients with lower MVD which may suggest that uPAR can be correlated with progression of colorectal cancer. The significant relationship between the high MVD and uPAR antigen level appeared to be independent of the (CA)n repeat polymorphism because no differences in the level of uPAR antigen between carriers of alleles were found. The received results, indicate that uPAR might be considered as a target in colorectal cancer patients' therapy

Association of Polymorphism of Lys589glu Exo1 Gene with the Risk of Colorectal Cancer in the Polish Population

The incidence of colorectal cancer (CRC) is increasing from year to year. Despite intensive research CRC etiology remains unknown. Studies suggest that at the basis of the process of carcinogenesis can lie reduced efficiency of DNA repair mechanisms, often caused by polymorphisms in DNA repair genes. The aim of the study was to determine the relationship between gene polymorphism Lys589Glu of EXO1 gene and modulation of the risk of colorectal cancer in the Polish population. Determination of the molecular basis of carcinogenesis process and predicting increased risk will allow qualifying patients to increased risk group and including them in preventive program. Material and methods. The material used in study was blood collected from 130 patients diagnosed with colorectal cancer. The control group consisted of 135 healthy people. Genotyping was performed by TaqMan method. Results. The results obtained indicate that the genotype Lys/Glu is associated with an increased risk of colorectal cancer (OR 1.811, 95% Cl 1.031-3.181, p = 0.038). Conclusion. On the basis of these results, we conclude that Exo1 gene polymorphism Lys589Glu may be associated with an increased risk of colorectal cancer

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&ndash;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&ndash;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

Tumour protein 53 is linked with type 2 diabetes mellitus

Background & objectives: Tumour protein p53 (TP53) is a stress sensitive transcription factor responsible for the control of cell survival and death to prevent from tumour formation. In vitro and animal studies have indicated that TP53 also responds to metabolic changes and influences metabolic pathways. This study was undertaken to determine the serum level of TP53 and its correlations with clinical and biochemical parameters in type 2 diabetes mellitus (T2DM) patients in comparison to non-diabetic control individuals. Methods: An observational study was conducted between December 2009 and November 2013 to evaluate TP53 serum level using ELISA. Cases (n=225) were defined as patients who were diagnosed with T2DM. Non-diabetic controls (n=255) were matched by age and sex. Multivariable modelling using logistic regression examined associations between clinical characteristics and TP53 level or T2DM predication was performed. Results: Serum TP53 level was significantly higher in T2DM patients as compared to non-diabetic healthy controls (1.69 vs 2.07 ng/ml, P<0.001). In T2DM patients, the level of TP53 increased with the age, duration of diabetes and waist-to-hip ratio (WHR) value. A logistic regression analysis revealed that increased serum TP53 level was significantly associated with family history of diabetes, age and WHR. Moreover, TP53, triglyceride and body mass index could be used to predict T2DM. Interpretation & conclusions: Our results suggest that TP53 may be linked with T2DM. The fluctuations of serum TP53 level may reflect metabolic and oxidative stress associated with chronic hyperglycaemia. Further studies need to be done to confirm these findings