Clinical significance of genetic variations in the PI3K/PTEN/AKT/mTOR pathway in Korean patients with colorectal cancer

Oncology. 2010;79(3-4):278-82. doi: 10.1159/000320761. Epub 2011 Mar 16.

Abstract

Objective: Signaling through the PI3K/PTEN/AKT/mTOR pathway is responsible for balancing cell survival and apoptosis. Accordingly, the present study analyzed 14 SNPs of the PI3K/PTEN/AKT/mTOR pathway genes and their impact on the prognosis for patients with colorectal cancer.

Methods: 444 consecutive patients with surgically resected colorectal adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from fresh colorectal tissue, and 14 polymorphisms of the PI3K/PTEN/AKT/mTOR pathway genes were determined using a real-time PCR genotyping assay.

Results: Pathologic stages after surgery were as follows: stage 0/I (n = 85, 19.1%), stage II (n = 149, 33.6%), stage III (n = 147, 33.1%), and stage IV (n = 63, 14.2%). Univariate and multivariate survival analysis including stage, age, site of disease, adjuvant chemotherapy, and carcinoembryonic antigen (CEA) level showed that these polymorphisms were not associated with progression-free or overall survival. For the clinicopathologic parameters, CEA level and TNM stage were significant prognostic factors in a Cox model for survival.

Conclusion: None of the 14 SNPs of the PI3K/PTEN/AKT/mTOR pathway genes investigated in this study was found to be an independent prognostic marker for Korean patients with surgically resected colorectal cancer.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Aged, 80 and over
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / surgery
  • DNA, Neoplasm / genetics
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • PTEN Phosphohydrolase / genetics*
  • Phosphatidylinositol 3-Kinases / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Proto-Oncogene Proteins c-akt / genetics*
  • Signal Transduction
  • Survival Rate
  • TOR Serine-Threonine Kinases / genetics*
  • Young Adult

Substances

  • DNA, Neoplasm
  • MTOR protein, human
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • PTEN Phosphohydrolase
  • PTEN protein, human