Dataset Information

The influence of glyoxalase 1 gene polymorphism on its expression at different stages of breast cancer in Egyptian women.

ABSTRACT: Aim:To assess the association of GLO1 C332C gene polymorphism with breast cancer risk at different stages of the disease and to investigate the effect of this gene polymorphism on its mRNA expression and enzyme activity. Methods:GLO1 C332C gene polymorphism was analyzed by PCR-RFLP in 100 healthy controls and 200 patients with breast cancer (100 patients with stage I & II and 100 patients with stage III & IV). GLO1 mRNA expression was measured by real time PCR. Serum GLO1 enzyme activity was measured colorimetrically. Results:GLO1 A allele was associated with increased risk of breast cancer [OR (95%CI)= 2.8(1.9-4.1), P < 0.001]. Its frequency was significantly higher among advanced stages of breast cancer compared with localized tumors (OR (95%CI)= 1.9(1.3-2.9), p < 0.001). GLO1 mRNA expression and enzyme activity were significantly higher in breast cancer patients compared to controls and they were much higher in the advanced stages of the disease (P < 0.001). Carriers of AA genotype showed higher GLO1 expression and enzyme activity compared with carriers of CC genotype. Conclusion:GLO1 C332C SNP was associated with overexpression of GLO1 mRNA and higher enzyme activity in breast cancer patients suggesting its role in the development of breast cancer and its progression from localized to advanced.

SUBMITTER: Abdul-Maksoud RS

PROVIDER: S-EPMC5755725 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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The influence of glyoxalase 1 gene polymorphism on its expression at different stages of breast cancer in Egyptian women.

Abdul-Maksoud Rehab S RS Elsayed Walid Sh WS Elsayed Rasha S RS

Genes & cancer 20171101 11-12

<h4>Aim</h4>To assess the association of GLO1 C332C gene polymorphism with breast cancer risk at different stages of the disease and to investigate the effect of this gene polymorphism on its mRNA expression and enzyme activity.<h4>Methods</h4>GLO1 C332C gene polymorphism was analyzed by PCR-RFLP in 100 healthy controls and 200 patients with breast cancer (100 patients with stage I & II and 100 patients with stage III & IV). GLO1 mRNA expression was measured by real time PCR. Serum GLO1 enzyme a ...[more]

PMID: 29321821

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Project description:BackgroundNestin is a neural stem cell protein that plays an important role in cancer stem cells (CSC) development and proliferation. It has been identified as a marker for newly formed endothelial cells and was shown to be preferentially expressed in basal and myoepithelial cells of the mammary gland. HOTAIR is long intergenic non-coding (linRNA) associated with tumorigenesis through promotion of epithelial-mesenchymal transition (EMT) and stemness as well. HOTAIR gene contains a functioning single nucleotide polymorphic site rs12826786 C>T that has been associated with several cancer types.MethodsWe evaluated serum Nestin and the HOTAIR rs12826786 C>T polymorphism in healthy Egyptian women and those with breast cancer as a possible screening tool to identify patients with breast cancer. Also, we tested the possible association of the two markers with each other and the aggressiveness of the disease.ResultsPatients with breast cancer had a median (Min-Max) of serum Nestin 31.3 (6.7-167.3 pg/mL), while control subjects had a median (Min-Max) of serum Nestin 42.3 (25.7-315.95) pg/mL. The best cut-off value for serum Nestin to differentiate normal subjects and patients with breast cancer was 39.9 pg/mL. This cut-off value had a diagnostic sensitivity of 84.8% and specificity of 65.1%. There was a significant difference in the distribution of different alleles in patients with breast cancer than normal subjects (P=0.039 Exact Fisher test). The breast cancer patients group had 23.9% CC, 52.1% CT, and 23.9% TT genotypes, respectively, while the control group had 46.9% CC, 42.8% CT, and 10.2% TT, respectively.ConclusionsA significantly low serum Nestin below 39.9 pg/mL and a higher percentage of the T/T homozygous variant allele of HOTAIR rs12826786 C>T were found in Egyptian patients with breast cancer. We suggest that the reported cut-off value of serum Nestin and the presence of C/T polymorphism can be used to assess the risk of females for developing breast cancer and might be of potential benefit in screening the disease. Larger studies in different ethnic groups are needed to confirm our findings.

Project description:Breast cancer is one of the primary threats to women's health worldwide. However, the molecular mechanisms underlying the development of breast cancer remain to be fully elucidated. The present study aimed to investigate specific target gene expression profiles in breast cancer tissues in general and in different breast cancer stages, as well as to explore their functions in tumor development. For integrated analysis, a total of 5 gene expression profiling datasets for 3 different stages of breast cancer (stages I-III) were downloaded from the Gene Expression Omnibus of the National Center for Biotechnology Information. Pre-processing of these datasets was performed using the Robust Multi-array Average algorithm and global renormalization was performed for all studies. Differentially expressed genes between breast cancer patients and controls were estimated using the empirical Bayes algorithm. The Database for Annotation, Visualization and Integrated Discovery web server was used for analyzing the enrichment of the differentially expressed genes in Gene Ontology terms of the category biological process and in Kyoto Encyclopedia of Genes and Genomes pathways. Furthermore, breast cancer target genes were downloaded from the Thomson Reuters Integrity Database. We merged these target genes with the genes in breast cancer datasets. Analysis of anti-breast cancer gene networks was performed using the Genome-scale Integrated Analysis of Gene Networks in Tissues web server. The results demonstrated that the normal functions of the cell cycle, cell migration and cell adhesion were altered in all stages of breast cancer. Furthermore, 12 anti-breast cancer genes were identified to be dysregulated in at least one of the three stages. Among all of these genes, ribonucleotide reductase regulatory subunit M2 (RRM2) exhibited the highest degree of interaction with other interacting genes. Analysis of the network interactions revealed that the transcription factor of RRM2 is crucial for cancer development. Other genes, including mucin 1, progesterone receptor and cyclin-dependent kinase 5 regulatory subunit associated protein 3, also exhibited a high degree of interaction with the associated genes. In conclusion, several key anti-breast cancer genes identified in the present study are mainly associated with the regulation of the cell cycle, cell migration, cell adhesion and other cancer-associated cell functions, particularly RRM2.

Dataset Information

The influence of glyoxalase 1 gene polymorphism on its expression at different stages of breast cancer in Egyptian women.

Publications

The influence of glyoxalase 1 gene polymorphism on its expression at different stages of breast cancer in Egyptian women.

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