Evaluation of MTHFR677C>T 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) 677C>T may have oncogenic role through disruption of normal DNA methylation pattern, synthesis, and impaired DNA repair. MTHFR677C>T or A222V (rs1801133) polymorphism has conflicting role in susceptibility to ESCC among different populations. Thus, we aimed to study the role of MTHFR677C>T 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 MTHFR677C>T 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 MTHFR677C>T polymorphism in ESCC patients. In conclusion, MTHFR677C>T polymorphism does not seem to have significant role either in susceptibility or survival of ESCC in a northern Indian population.