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Tumor Biology

, Volume 36, Issue 7, pp 5635–5639 | Cite as

Genome-wide association pathway analysis to identify candidate single nucleotide polymorphisms and molecular pathways for gastric adenocarcinoma

  • Hongcheng Zhu
  • Meilin Yang
  • Hao Zhang
  • Xiaochen Chen
  • Xi Yang
  • Chi Zhang
  • Qin Qin
  • Hongyan Cheng
  • Xinchen Sun
Research Article

Abstract

To demonstrate candidate single nucleotide polymorphisms that might affect susceptibility to gastric adenocarcinoma as well as their potential mechanisms and pathway hypotheses, we performed a genome-wide association study dataset of gastric adenocarcinoma. Our study included 472,342 single nucleotide polymorphisms from 2766 cases of gastric cardia adenocarcinoma cases and 11,013 subjects from north central China as control groups. The identify candidate causal SNPs and pathways (ICSNPathway) analysis was employed to identify 13 candidate single nucleotide polymorphisms, nine genes, and 15 pathways. The top three candidate SNPs were rs3765524 (−log10(p) = 8.556), rs2274223 (−log10(p) = 8.633), and rs2076472 (−log10(p) = 3.205). The strongest mechanism involved the modulation of rs4745 and rs12904, thereby affecting their regulatory roles in ephrin receptor binding (p = 0.001; FDR = 0.005). The second strongest hypothetical biological mechanism was that rs932972 and rs1052177 alters the regulatory role of the glycolysis pathway (p < 0.001; FDR = 0.013). The most significant pathway was the regulation of the ephrin receptor binding pathway, which involved EFNA1, TIAM1, EFNA5, EFNB2, and EFNB3.

Keywords

Genome-wide association Pathway analysis Single-nucleotide polymorphisms Gastric adenocarcinoma 

Notes

Acknowledgments

This work was supported by the Natural Science Foundation of China (No. 81272504), Innovation Team [No. LJ201123 (EH11)], A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) (JX10231801), grants from Key Academic Discipline of Jiangsu Province “Medical Aspects of Specific Environments”, Six Major Talent Peak Project of Jiangsu Province (2013-WSN-040), Research and Innovation Project for College Graduates of Jiangsu Province (KYLX_0955).

Conflicts of interest

None

Supplementary material

13277_2015_3236_MOESM1_ESM.doc (26 kb)
Supplementary Table 1 (DOC 26 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Hongcheng Zhu
    • 1
  • Meilin Yang
    • 1
  • Hao Zhang
    • 1
  • Xiaochen Chen
    • 1
  • Xi Yang
    • 1
  • Chi Zhang
    • 1
  • Qin Qin
    • 1
  • Hongyan Cheng
    • 2
  • Xinchen Sun
    • 1
  1. 1.Department of Radiation OncologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  2. 2.Department of General Internal MedicineThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina

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