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

Guowen Ding; Yafeng Wang; Yu Chen; Jun Yin; Chao Liu; Yu Fan; Hao Qiu; Weifeng Tang; Shuchen Chen

doi:10.18632/oncotarget.22845

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

Oncotarget. 2017 Dec 1;8(67):111482-111494. doi: 10.18632/oncotarget.22845. eCollection 2017 Dec 19.

Authors

Guowen Ding¹, Yafeng Wang², Yu Chen³, Jun Yin¹, Chao Liu¹, Yu Fan⁴, Hao Qiu⁵, Weifeng Tang⁶, Shuchen Chen⁶

Affiliations

¹ Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China.
² Department of Cardiology, The People's Hospital of Xishuangbanna Dai Autonomous Prefecture, Jinghong, Yunnan Province, China.
³ Department of Medical Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, Fujian Province, China.
⁴ Department of Medical Oncology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China.
⁵ Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, China.
⁶ Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China.

Abstract

In this study, we aimed to determine the potential association of MTHFR tagging single nucleotide polymorphisms (SNPs) with risk of developing esophagogastric junction adenocarcinoma (EGJA). MTHFR 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 MTHFR rs1801133 G>A polymorphism was significantly associated with the risk of developing EGJA (AA vs. GG: adjusted P = 0.001; GA/AA vs. GG: adjusted P = 0.007 and AA vs. GA/GG: adjusted P = 0.001). However, for MTHFR rs4845882 G>A polymorphism, the decreased risk of EGJA was found in two genetic models (AA vs. GG: adjusted P = 0.002 and AA vs. GA/GG: adjusted P = 0.005). In addition, for MTHFR 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 MTHFR G_rs1801133T_rs3753584G_rs4845882A_rs4846048C_rs9651118, G_rs1801133C_rs3753584A_rs4845882A_rs4846048T_rs9651118 and G_rs1801133T_rs3753584A_rs4845882G_rs4846048T_rs9651118 haplotypes significantly decreased the risk of EGJA (P = 0.002, P < 0.001 and P = 0.038, respectively). In conclusion, our study demonstrates that MTHFR rs1801133 G>A may be associated with the increased risk of EGJA. Meanwhile, MTHFR 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.

Keywords: MTHFR; esophagogastric junction adenocarcinoma; polymorphism; risk.