A study of the MTHFR gene polymorphism C677T in colorectal cancer.
OBJECTIVE
The aim of this study was to examine the clinical significance of the methylenetetrahydrofolate reductase (MTHFR) gene polymorphism C677T in colorectal cancer (CRC). The hypothesis was that the genotype could affect the risk of cancer development and the results of cancer treatment.


METHODS
Genotyping was made for a random 30% (n = 544) of all patients treated for CRC at our unit from 1999 to 2006 (n = 1812). Basic clinical and pathologic factors were analyzed by genotype group and also compared with those of the entire cohort. Tolerability of chemotherapy and possible side effects were analyzed by genotype. Survival was analyzed by genotype for all stages for patients treated between 1999 and 2003. The genotype prevalence was also compared with a control material of healthy blood donors.


RESULTS
No genotype was associated with an increased risk of CRC or higher cancer stage. The patients with CT/TT genotype had significantly greater risk of suffering side effects from fluoropyrimidine (5-fluorouracil) treatment (P < .05). In stage III colon cancer, the patients with CT/TT genotype had a poorer prognosis than those with the CC genotype. The difference was significant in univariate (P < .003) and multivariate (P < .040) analysis. Though the genotype-associated side effect risks remained in stage IV, the effect on survival was not significant (P < .1).


CONCLUSIONS
The MTHFR polymorphism C677T does, in our material, not affect the risk of CRC; however, it can affect the sensitivity to chemotherapy and the risk of side-effects and therefore survival in stage III and possibly stage IV colon cancer. It could be a future predictive factor in the choice of a treatment regimen.
Derwinger
Kristoffer
K
Department of Surgery, Sahlgrenska University Hospital/Ostra, Gothenburg, Sweden. kristoffer.derwinger@vgregion.se
Wettergren
Yvonne
Y
Odin
Elisabeth
E
Carlsson
Göran
G
Gustavsson
Bengt
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D016019:Survival Analysis
D042965:Methylenetetrahydrofolate Reductase (NADPH2)