Polymorphisms of folate pathway enzymes (methylenetetrahydrofolate reductase and thymidylate synthase) and their relationship with thymidylate synthase expression in human astrocytic tumors. 2012

Débora Menezes da Costa, and Germano Paulo Venceslau de Lima, and Mário Henrique Girão Faria, and Silvia Helena Barem Rabenhorst
Molecular Genetics Laboratory, Department of Pathology and Forensic Medicine, School of Medicine, Federal University of Ceará, Fortaleza, Ceara, Brazil.

Two important polymorphisms of folate cycle enzymes, methylenetetrahydrofolate reductase (MTHFR) C677T and thymidylate synthase (TS) enhancer region (TSER) 28-bp tandem repeat, are related to risk of various types of cancer, including brain tumors, although there are few studies on this subject. A case-control study of these two polymorphisms in astrocytomas of different grades was carried out using polymerase chain reaction-restriction fragment length polymorphism, also determining the immunohistochemical expression of TS. The MTHFR 677 TT genotype was less associated with astrocytic tumors (odds ratio [OR]=0.00; p=0.0238), but the TSER polymorphism did not show any significant association. Combined genotype TT-double repeats/triple repeats (2R/3R) had a protective effect against astrocytomas (OR=0.00; p=0.0388). Expression of TS protein was observed in the majority of cases, with grade IV tumors being the exception. Moreover, the median H-score for the pilocytic astrocytomas was significantly higher when compared with that for diffuse tumors. There was an inverse correlation between the 2R/2R genotype and the highest TS-expressing tumors, and 3R/3R was relatively more frequent among the tumors grouped in the third and fourth quartiles. Our results provide support for the role of MTHFR and TS polymorphism in gliomagenesis, possibly because of the alteration of DNA methylation and repair status. Moreover, high levels of TS expression were detected in these tumors.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008297 Male Males
D011110 Polymorphism, Genetic The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level. Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D012150 Polymorphism, Restriction Fragment Length Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment. RFLP,Restriction Fragment Length Polymorphism,RFLPs,Restriction Fragment Length Polymorphisms
D004742 Enhancer Elements, Genetic Cis-acting DNA sequences which can increase transcription of genes. Enhancers can usually function in either orientation and at various distances from a promoter. Enhancer Elements,Enhancer Sequences,Element, Enhancer,Element, Genetic Enhancer,Elements, Enhancer,Elements, Genetic Enhancer,Enhancer Element,Enhancer Element, Genetic,Enhancer Sequence,Genetic Enhancer Element,Genetic Enhancer Elements,Sequence, Enhancer,Sequences, Enhancer
D005260 Female Females
D005787 Gene Frequency The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION. Allele Frequency,Genetic Equilibrium,Equilibrium, Genetic,Allele Frequencies,Frequencies, Allele,Frequencies, Gene,Frequency, Allele,Frequency, Gene,Gene Frequencies
D005838 Genotype The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS. Genogroup,Genogroups,Genotypes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001254 Astrocytoma Neoplasms of the brain and spinal cord derived from glial cells which vary from histologically benign forms to highly anaplastic and malignant tumors. Fibrillary astrocytomas are the most common type and may be classified in order of increasing malignancy (grades I through IV). In the first two decades of life, astrocytomas tend to originate in the cerebellar hemispheres; in adults, they most frequently arise in the cerebrum and frequently undergo malignant transformation. (From Devita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2013-7; Holland et al., Cancer Medicine, 3d ed, p1082) Astrocytoma, Subependymal Giant Cell,Glioma, Astrocytic,Oligoastrocytoma, Mixed,Pleomorphic Xanthoastrocytomas,Anaplastic Astrocytoma,Astrocytoma, Grade I,Astrocytoma, Grade II,Astrocytoma, Grade III,Astrocytoma, Protoplasmic,Astroglioma,Cerebral Astrocytoma,Childhood Cerebral Astrocytoma,Fibrillary Astrocytoma,Gemistocytic Astrocytoma,Intracranial Astrocytoma,Juvenile Pilocytic Astrocytoma,Pilocytic Astrocytoma,Subependymal Giant Cell Astrocytoma,Anaplastic Astrocytomas,Astrocytic Glioma,Astrocytic Gliomas,Astrocytoma, Anaplastic,Astrocytoma, Cerebral,Astrocytoma, Childhood Cerebral,Astrocytoma, Fibrillary,Astrocytoma, Gemistocytic,Astrocytoma, Intracranial,Astrocytoma, Juvenile Pilocytic,Astrocytoma, Pilocytic,Astrocytomas,Astrocytomas, Grade III,Astrogliomas,Cerebral Astrocytoma, Childhood,Cerebral Astrocytomas,Childhood Cerebral Astrocytomas,Fibrillary Astrocytomas,Gemistocytic Astrocytomas,Gliomas, Astrocytic,Grade I Astrocytoma,Grade I Astrocytomas,Grade II Astrocytoma,Grade II Astrocytomas,Grade III Astrocytoma,Grade III Astrocytomas,Intracranial Astrocytomas,Juvenile Pilocytic Astrocytomas,Mixed Oligoastrocytoma,Mixed Oligoastrocytomas,Pilocytic Astrocytoma, Juvenile,Pilocytic Astrocytomas,Pleomorphic Xanthoastrocytoma,Protoplasmic Astrocytoma,Protoplasmic Astrocytomas,Xanthoastrocytoma, Pleomorphic

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