| Author/Editor | Lodrant, Sabina | |
| Title | Polimorfizmi genov za encime v presnovni poti folata in pojav mikrosatelitne nestabilnosti DNK pri bolnikih z rakom debelega črevesa | |
| Type | monografija | |
| Place | Ljubljana | |
| Publisher | Univerza v Ljubljani, Medicinska fakulteta | |
| Publication year | 2005 | |
| Volume | str. 59 | |
| Language | slo | |
| Abstract | Background Folate is a universal donor of one-carbon functional groups in cells and sufficient amounts of this vitamin are crucial for normal cell growth and replication. Four enzymes are of particular importance in the metabolism of folate: methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MS), methionine synthase reductase (MTRR) and thymidilate synthase (TS). Polymorphic sites that affect the activity of these enzymes have been found in their genes. The altered enzymatic activity leads to insufficient nucleotide synthesis and changes in DNA methylation, which can result in the development of microsatellite instability (MSI). Aims To establish, if polymorphic genes coding for enzymes in the metabolic pathway of folate modify the risk of MSI in patients with colorectal cancer (CRC), we compared the frequencies of polymorphic genotypes between CRC patients with and without MSI. Methods Genotyping approach, based on polymerase chain reaction (PCR) and restriction analyses of amplified DNA fragments, was used. Our test group included 35 CRC patients with MSI, while 137 matched CRC patients without MSI comprised the control group. Results The MS 2756GG polymorphic genotype represented a risk factor for the development of MSI in our group of patients (odds ratio; OR=6,3, 95%CI=1,86-13,1). On the contrary the polymorphism in the promoter region of TS protected from the development of MSI (odds ratio; OR=0,46, 95%CI=0,2-1,06). The frequencies of other polymorphic genotypes did not differ significantly between the MSI and MSS group of patients (test x2; MTHFR677: x2=1,26, m=2, p= 0,53, MTHFR1298: x2=0,47, m=2, p=0,79 and MTRR 66: x2=0,56, m=2, p=0,75). Conclusions The polymorphism in the gene for MS increased the risk for MSI 6,3 fold; while the polymorphism of TS promoter region reduced the risk for MSI 2,2 fold. (Abstract truncated at 2000 characters) | |
| Descriptors | COLONIC NEOPLASMS GENOTYPE FOLIC ACID METHYLENETETRAHYDROFOLATE DEHYDROGENASE TETRAHYDROPTEROYLGLUTAMATE METHYLTRANSFERASE THYMIDINE KINASE POLYMERASE CHAIN REACTION MICROSATELLITE REPEATS |