Methylenetetrahydrofolate reductase tagging polymorphisms are associated with risk of esophagogastric junction adenocarcinoma: a case-control study involving 2,740 Chinese Han subjects
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Guowen Ding1,*, Yafeng Wang2,*, Yu Chen3,*, Jun Yin1, Chao Liu1, Yu Fan4, Hao Qiu5, Weifeng Tang6 and Shuchen Chen6
1Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China
2Department of Cardiology, The People’s Hospital of Xishuangbanna Dai Autonomous Prefecture, Jinghong, Yunnan Province, China
3Department of Medical Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, Fujian Province, China
4Department of Medical Oncology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China
5Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, China
6Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
*These authors have contributed equally to this work
Shuchen Chen, email: email@example.com
Weifeng Tang, email: firstname.lastname@example.org
Keywords: MTHFR; polymorphism; esophagogastric junction adenocarcinoma; risk
Received: May 16, 2017 Accepted: November 13, 2017 Published: December 01, 2017
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 Grs1801133Trs3753584Grs4845882Ars4846048Crs9651118, Grs1801133Crs3753584Ars4845882Ars4846048Trs9651118 and Grs1801133Trs3753584Ars4845882Grs4846048Trs9651118 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.
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