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

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

Genetic Variations of the CTNNA1 And The CTNNB1 Genes in Sporadic Colorectal Cancer in Polish Population

Experimental as well as clinical observations have demonstrated that the E-cadherin/catenin complex is a powerful inhibitor of invasion. Abrogation of this pathway is implicated in the carcinogenesis of several malignancies, especially colorectal cancer. The aim of the study was to determine the CTNNA1 and the CTNNB1 mutations and its relationship to clinical and pathological features of sporadic colorectal cancer (CRC) in Polish patients. Material and methods. Paired tumor and normal tissue samples from 110 sporadic CRC patients undergoing resective surgery were prospectively studied for the alpha catenin (CTNNA1) gene and beta catenin (CTNNB1)gene mutations by PCR/single strand conformation polymorphism (SSCP). Results. The CTNNA1 gene alteration in exon 7 were detected in 4 samples and in exon 3 of CTNNB1 gene were found in 3 samples. There was a trend at the limit of statistical significance associating younger age at diagnosis (<50) with CTNNA1 and the CTNNB1 mutations. The mutation of CTNNB1 seemed to occur more frequently in the proximal colon than distal. The CRC patients with CTNNA1 mutation had a significantly increased lymph node metastasis. On the other hand, there was no correlation between mutations and the other clinical variables (e.g. sex, grade and depth of invasion). Conclusion. Although we found a low frequency of mutations in the CTNNA1 and the CTNNB1 genes, but the analysis the relationship with clinical and pathological features of CRC patients may indicated an association of these mutations with the risk and progression of CRC

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

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

Analysis of the G/C polymorphism in the 5'-untranslated region of the RAD51 gene in breast cancer.

The breast cancer suppressor proteins BRCA1 and BRCA2 interact with RAD51, a protein essential for maintaining genomic stability by playing a central role in homology-dependent recombinational repair of the DNA double-strand breaks. Therefore, genetic variability in the RAD51 gene may contribute to the appearance and/or progression of breast cancer. A single nucleotide polymorphism in the 5'- untranslated region of RAD51 (a G to C substitution at position 135, the G/C polymorphism) is reported to modulate breast cancer risk. We investigated the distribution of genotypes and frequency of alleles of the G/C polymorphism in breast cancer. Tumor tissues were obtained from postmenopausal women with node-negative and node-positive breast carcinoma with uniform tumor size. Blood samples from age matched healthy women served as control. The G/C polymorphism was determined by PCR-based MvaI restriction fragment length polymorphism. The distribution of the genotypes of the G/C polymorphism did not differ significantly (P >0.05) from those predicted by the Hardy-Weinberg distribution. There were no differences in the genotype distribution and allele frequencies between node-positive and node-negative patients. There were no significant differences between distributions of the genotypes in subgroups assigned to histological grades according to Scarf-Bloom-Richardson criteria and the distribution predicted by Hardy-Weinberg equilibrium (P >0.05). Our study implies that the G/C polymorphism of the RAD51 gene may not be directly involved in the development and/or progression of breast cancer and so it may not be useful as an independent marker in this disease