A GG allele of 3'-side AKT1 SNP is associated with decreased AKT1 activation and better prognosis of gastric cancer

J Cancer Res Clin Oncol. 2014 Aug;140(8):1399-411. doi: 10.1007/s00432-014-1663-x. Epub 2014 Apr 16.


Purpose: v-akt Murine thymoma viral oncogene homolog (AKT) pathway is critically involved in cancer cell growth, invasion, and survival. We examined the correlation between the genetic variations in molecules of AKT pathway and clinical outcomes of gastric cancer.

Patients and methods: Six single nucleotide polymorphisms (SNPs) located in the four core genes of AKT pathway, namely the PIK3CA, PTEN, AKT1, and mTOR, were determined in 221 patients with stage T2 and T3 gastric cancer. Additionally, the activation of AKT1 in gastric cancer tissues was examined by immunostaining. The correlation between SNPs, AKT activation, and the progress of gastric cancer was analyzed after an average of 51-month follow-up.

Results: The overall recurrence and survival rate in this study group were 54.8 and 46.6 %, respectively. The recurrence rate was reduced 30.4 %, and the survival rate was increased 33.7 % in patients with GG allele of a 3'-side AKT1 SNP (rs2498804). Significantly, GG allele was associated with lower AKT1 activation in gastric cancer tissues. On the contrary, CC allele of PTEN (rs701848) was associated with the increased risk of recurrence (hazard ratio [HR] 2.06, 95 % CI 1.19-3.58) and patient death (HR 2.01, 95 % CI 1.15-3.53).

Conclusions: The genetic variants in the PI3K/PTEN/AKT especially the GG allele in 3' side of AKT1 are closely related to clinical outcomes of gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / enzymology
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / therapy
  • Base Sequence
  • Binding Sites
  • Class I Phosphatidylinositol 3-Kinases
  • Combined Modality Therapy
  • Disease-Free Survival
  • Enzyme Activation
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / genetics
  • Middle Aged
  • Neoplasm Recurrence, Local / enzymology
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / prevention & control
  • PTEN Phosphohydrolase / genetics
  • Phosphatidylinositol 3-Kinases / genetics
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Proto-Oncogene Proteins c-akt / genetics*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Stomach Neoplasms / enzymology
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / therapy
  • Treatment Outcome


  • MIRN20a microRNA, human
  • MicroRNAs
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human