C677T and A1298C mutations in the MTHFR gene and survival in colorectal cancer.
OBJECTIVE
Our preliminary results laboratory have shown some association between C677T and A1298C MTHFR mutations and factors influencing survival in colorectal cancer. We studied the survival of patients with colorectal cancer depending on the initial Dukes-MAC stage of the disease at the time of diagnosis and the MTHFR mutation present.


METHODS
We randomly selected 69 patients with sporadic colorectal cancer who underwent surgery at the Surgical Clinic III Cluj between October 2003 and May 2005. The study ended on 15 March 2008. Survival data was verified in 48 cases. Survival analyses were performed using Kaplan-Mayer survival curves and median survival time was calculated. The comparison of two or more categories was performed using the Logrank test, considering the threshold value p less or equal to 0.05.


RESULTS
In both stage B and C patients with the CT/TT mutation have a poorer survival rate than those with the wild CC genotype (p less than 0.05). The presence of the C677T mutation (CT or TT genotype) in patients diagnosed in stage D did not result as a significant survival risk factor (HR=0.537, 95% CI 0.128-2.184) p>0.05. Patients diagnosed with stage C colorectal cancer, who have the 1298C allele, have significantly better survival than those without this allele, 60% vs. 15.4%, (p=0.0016).


CONCLUSIONS
In our study in both stage B and C, patients with the CT/TT mutation have poorer survival than the wild CC genotype. In stage B patients, the A1298C mutation is a negative prognostic factor. The presence of the A1298C mutation in a hetero- or homozygous form plays a protective role in stage C.
Osian
Gelu
G
3rd Surgical Department, 19-21 Croitorilor Str, 400162 Cluj-Napoca, Romania. geluosian@yahoo.com
Procopciuc
Lucia
L
Vlad
Liviu
L
Iancu
Cornel
C
Mocan
Teodora
T
Mocan
Lucian
L
D000368:Aged; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality* / Q000601:surgery; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D042965:Methylenetetrahydrofolate Reductase (NADPH2)