Evaluation of MTHFR677CT Polymorphism in Prediction and Prognosis of Esophageal Squamous Cell Carcinoma: A Case-Control Study in a Northern Indian Population

Early diagnosis and better prognosis of esophageal squamous cell carcinoma (ESCC) is still a challenge. Besides environmental risk factors, nutritional deficiencies have an established role in pathogenesis of ESCC. Folate deficiency and functional polymorphisms in folate metabolizing genes such as methylene tetrahydrofolate reductase (MTHFR) 677CT may have oncogenic role through disruption of normal DNA methylation pattern, synthesis, and impaired DNA repair. MTHFR677CT or A222V (rs1801133) polymorphism has conflicting role in susceptibility to ESCC among different populations. Thus, we aimed to study the role of MTHFR677CT polymorphism in susceptibility, survival, and interaction with environmental risk factors in ESCC patients from a northern Indian population. A case control study was performed in 208 ESCC incident cases (including 114 follow-up cases) and 223 healthy controls, and genotyping was done by PCR-RFLP. Our results show no significant association of MTHFR677CT polymorphism with ESCC, tumor locations, or gender of subjects. However, we found a trend of decreased risk of ESCC due to interaction of MTHFR677CT genotype with smoking and alcohol intake. Kaplan Meier, and Cox regression survival analysis showed no prognostic impact of MTHFR677CT polymorphism in ESCC patients. In conclusion, MTHFR677CT polymorphism does not seem to have significant role either in susceptibility or survival of ESCC in a northern Indian population.