Abstract | BACKGROUND: AIM: To investigate the frequencies of the TT and 844ins68 genotypes in CRC patients with MSI+ tumours compared with those with MSI- tumours and a control population. SUBJECTS: Patients with CRC (n=501) and healthy control subjects (n=1207) were studied. CRC cases were classified as MSI+ (n=75) or MSI- (n=426) based on deletions within the BAT-26 mononucleotide repeat. METHODS: Subjects were genotyped for MTHFR using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and PCR-restriction fragment length polymorphism (PCR-RFLP) techniques, and for CBS using PCR. RESULTS: The MTHFR TT genotype was more frequent in older CRC patients (>or=70 y) compared with equivalent aged controls (p=0.03), was associated with a significantly later age of diagnosis in patients with proximal colon tumours (p=0.02), and was almost twice as frequent in MSI+ than in MSI- tumours (p=0.05). Compared with normal controls, the 844ins68 variant of CBS was less frequent in patients with proximal tumours (p=0.02). CONCLUSIONS: The TT genotype of MTHFR is associated with an increased risk of CRC in older populations, possibly due to age related disturbances in folate metabolism. The TT genotype appears to predispose to CRC that is MSI+. This may reflect the involvement of aberrant DNA methylation frequently associated with MSI+. The 844ins68 CBS polymorphism may protect against proximal tumours.
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Authors | B Shannon, S Gnanasampanthan, J Beilby, B Iacopetta |
Journal | Gut
(Gut)
Vol. 50
Issue 4
Pg. 520-4
(Apr 2002)
ISSN: 0017-5749 [Print] England |
PMID | 11889073
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Oxidoreductases Acting on CH-NH Group Donors
- Methylenetetrahydrofolate Reductase (NADPH2)
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Colorectal Neoplasms
(genetics)
- Genotype
- Heterozygote
- Humans
- Methylenetetrahydrofolate Reductase (NADPH2)
- Microsatellite Repeats
- Middle Aged
- Oxidoreductases Acting on CH-NH Group Donors
(genetics)
- Polymorphism, Genetic
- Prognosis
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