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Expression and clinical significance of methylenetetrahydrofolate reductase in patients with colorectal cancer

Odin, Elisabeth, 1955 (författare)
Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences
Wettergren, Yvonne, 1957 (författare)
Carlsson, Göran, 1951 (författare)
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Danenberg, Peter (författare)
Termini, Angelo, 1963 (författare)
Willen, Roger, 1939 (författare)
Gustavsson, Bengt, 1947 (författare)
Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences
Willén, Roger (författare)
Uppsala universitet,Institutionen för genetik och patologi
Danenberg, Peter V. (författare)
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2006
2006
Engelska.
Ingår i: Clin Colorectal Cancer. - 1533-0028. ; 5:5, s. 344-9
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • BACKGROUND: The aim of the study was to investigate the influence of methylenetetrahydrofolate reductase (MTHFR) gene expression levels and MTHFR polymorphism C677T on the outcome of patients with colorectal cancer (CRC). Furthermore, we wanted to evaluate the interaction between MTHFR and thymidylate synthase (TS) and folylpolyglutamate synthase (FPGS) and to investigate the impact of folate concentration on patients with CRC with different MTHFR genotypes. PATIENTS AND METHODS: The frequency of MTHFR polymorphism C677T was determined (n = 147), and gene expression levels of MTHFR, TS, and FPGS were quantified with real-time polymerase chain reaction (n = 157). Reduced folates in tissue were measured with a binding assay (n = 40). RESULTS: We observed a significantly lower concentration of tetrahydrofolate (THF) in patients with CT or TT genotypes compared with patients having the CC genotype. Twenty-six patients with Dukes A to C tumors who had not been subjected to chemotherapy relapsed. Out of these, 18 had CT or TT genotypes, and only 8 had the CC genotype (P = 0.045). Furthermore, 75 patients did not relapse, and out of these, 35 had CT or TT genotypes, and 40 had the CC genotype. The relative gene expression level of MTHFR in patients subgrouped by CC and CT or TT genotypes was significantly lower in carcinomas compared with adjacent mucosa (P < 0.0001 and P < 0.0001, respectively). A significant difference in MTHFR expression level was also observed according to MTHFR genotype in the tumor but not in adjacent mucosa. The MTHFR gene expression level in mucosa was a prognostic parameter independent of the clinicopathologic factors with regard to survival for patients with MTHFR C677T mutation. CONCLUSION: Our results showed that it is possible to identify patients with CRC with a higher risk for relapse. Furthermore, patients with a mutant genotype in combination with low MTHFR expression have a poor clinical outcome.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Nyckelord

Adult
Aged
Aged
80 and over
Carcinoma/genetics/*metabolism/*mortality
Colorectal Neoplasms/genetics/*metabolism/*mortality
Female
Folic Acid/genetics/metabolism
Gene Expression
Humans
Intestinal Mucosa/*metabolism
Male
Methylenetetrahydrofolate Reductase (NADPH2)/genetics/*metabolism
Middle Aged
RNA
Messenger/metabolism
Survival Rate
C677T
folate
folylpolyglutamate synthase
thymidylate synthase
MEDICINE
MEDICIN

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