In conclusion, this meta-analysis provides evidence that the MTHFRC677T polymorphism contributes to esophageal cancer development in Chinese populations.
Our findings supports the hypothesis that high folate intake and active MTHFRC677T polymorphism may exert protective roles in the prognosis of esophageal cancer in the Chinese population.
Cox regression revealed ypT category (P = 0.001) and lymphatic vessel invasion (P = 0.03) to be independent prognostic factors for esophageal cancer, and histopathological response (P = 0.01), MTHFR variant (rs1801131, P = 0.002), and ypN category (P = 0.02) to be prognostic factors for gastric cancer.
A significant association between the MTHFR 677 TT genotype and esophageal cancer was observed (OR=2.63, 95% CI: 1.75-3.94), although there was significant heterogeneity between studies.
The preliminary finding that methylenetetrahydrofolate reductase polymorphisms modify 5-fluorouracil response supports the hypothesis that response or resistance to therapy in esophageal cancer patients may be modulated by genetic variants involved in the metabolism or mechanism of chemotherapy drug action.
Folate consumption and MTHFR 677TT were associated with a non-significant tendency for decreased risk while the MTR genotypes did not show any links in themselves; further, when analysis was limited to heavy drinkers, the MTHFR TT genotype significantly decreased esophageal cancer risk [odds ratio (OR) = 0.27, 95% confidence interval (CI), 0.09-0.76].
These findings are generally consistent with our initial observation for esophageal cancer and suggest that the MTHFR genotype may be a determinant of GCA among this at-risk Chinese population.