Folate deficiency has been associated with certain types of human cancer. We therefore
investigated the effects of genetic polymorphisms in folate-metabolizing enzymes on the risk
of developing gastroesophageal cancers in a Chinese population where folate deficiency is
common. We found that functional polymorphisms in methylenetetrahydrofolate reductase
(MTHFR) and thymidylate synthase (TS), two key enzymes involved in folate and methyl
group metabolism, were significantly associated with increased risk of esophageal squamous
cell carcinoma, gastric cardia carcinoma, and pancreatic carcinoma. The polymorphisms
modulate risk of these cancers associated with low folate status. Our results suggest that
MTHFR and TS genotypes may be determinant of gastroesophageal cancers in this at-risk
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