C677T and A1298C Mutations in the MTHFR Gene and Survival in Colorectal Cancer
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Gelu Osian1, Lucia Procopciuc2, Liviu Vlad1, Cornel Iancu1, Teodora Mocan1, Lucian Mocan1
1) 3rd Surgical Department;
2) Biochemistry Department, University of Medicine and Pharmacy "Iuliu Hatieganu" Cluj-Napoca, Romania
Abstract
Background and aims: 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≤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<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.
Key words
MTHFR - colorectal cancer - survival.
