Methylenetetrahydrofolate reductase tagging polymorphisms are associated with risk of esophagogastric junction adenocarcinoma: a case-control study involving 2,740 Chinese Han subjects.

In this study, we aimed to determine the potential association of tagging single nucleotide polymorphisms (SNPs) with risk of developing esophagogastric junction adenocarcinoma (EGJA). rs1801133 G>A, rs3753584 T>C, rs4845882 G>A, rs4846048 A>G and rs9651118 T>C polymorphisms were genotyped in 1,677 healthy individuals and 1,063 patients with EGJA. We found that rs1801133 G>A polymorphism was significantly associated with the risk of developing EGJA (AA GG: adjusted = 0.001; GA/AA GG: adjusted = 0.007 and AA GA/GG: adjusted = 0.001). However, for rs4845882 G>A polymorphism, the decreased risk of EGJA was found in two genetic models (AA GG: adjusted = 0.002 and AA GA/GG: adjusted = 0.005). In addition, for rs3753584 T>C and rs9651118 T>C polymorphisms, a tendency to decreased risk of EGJA was noted. In a subgroup analysis, a significantly decreased risk of EGJA in <64 years subgroup was identified. We found that GTGAC, GCAAT and GTAGT haplotypes significantly decreased the risk of EGJA ( = 0.002, < 0.001 and = 0.038, respectively). In conclusion, our study demonstrates that rs1801133 G>A may be associated with the increased risk of EGJA. Meanwhile, rs3753584 T>C, rs4845882 G>A and rs9651118 T>C polymorphisms and haplotypes may decrease the risk of EGJA in Eastern Chinese Han population. Further studies with large sample size and detailed gene-environmental data are needed to validate our conclusion.