Abstract

IMPACT OF MTHFR C677T POLYMORPHISM AND PROTEIN EXPRESSION ON SURVIVAL AND 5-FU/OXALIPLATIN DRUG BASED TREATMENT IN COLORECTAL CANCER PATIENTS

Dr. Kinjal K. Gajjar, Dr. Toral H. Mandalia, Dr. Nandita R. Ghosh, Dr. Jayendrakumar B. Patel* and Dr. Hemangini H. Vora

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Abstract

Background: Methylene tetrahydrofolate reductase (MTHFR), a key enzyme in folate metabolism, plays an important role in 5-Flourouracil (5-FU) metabolic pathway. MTHFR C677T polymorphism has been associated with prognosis and 5-FU response in colorectal cancer (CRC) patients. Additionally, the enzymatic activity of MTHFR has been affected by this polymorphism. Hence, present study aimed to examine the role of MTHFR C677T polymorphism and MTHFR protein expression in colorectal cancer patients. Materials and Methods: MTHFR C677T polymorphism was studied by PCR-RFLP and MTHFR protein expression was examined by immunohistochemistry in 143 primary CRC patients. Further, results were associated with clinicopathological parameters and survival. The data was evaluated statistically using SPSS software. Results: MTHFR C677T polymorphism showed predominance of C/C wild type genotype (80%) as compared to variant C/T (16%) and T/T (4%) genotypes. Survival analysis demonstrated a significant reduced RFS and OS in patients with MTHFR C/T genotype as well as combined variant genotypes (C/T+T/T). Moreover, advanced stage and rectal cancer subgroups having C/T genotype; and female patients with C/T as well as combined variant genotypes were associated with unfavorable prognosis. The subgroup of patients treated with combined 5-FU+Oxaliplatin drug also showed reduced RFS and OS with C/T genotype as compared to those treated with 5-FU alone. Further, 75% of patients showed cytoplasmic MTHFR protein expression. However, no prognostic or predictive role of MTHFR protein expression was observed. Conclusion: MTHFR C677T polymorphism could be useful predictive and prognostic marker in CRC patients, while MTHFR protein expression had no clinical significance in studied patients.

Keywords: 5-FU, MTHFR C677T polymorphism, MTHFR protein expression, Immunohistochemistry, Prognosis, Colorectal cancer.