The GNAS SNP c.393C>T (rs7121) as a marker for disease progression and survival in cancer

Pharmacogenomics. 2019 May;20(7):553-562. doi: 10.2217/pgs-2018-0199.

Abstract

G-protein receptor signaling plays a key role in multiple signal transduction pathways. Aberrant activity of the stimulatory Gsα subunit has been frequently associated with cancer. GNAS sequence alterations and conformational changes of Gsα can both enhance or diminish its function and change downstream effects of G-protein receptor signaling. In this review and meta-analysis, we focus on the synonymous SNP rs7121 (FokI, c.393C>T), which is associated with either tumor progression or prolonged survival in cancer patients (overall hazard ratio = 2.256; p < 0.001). We finally point out the relevance of GNAS rs7121 as a promising biomarker and a prediction tool for therapy response and the need of further experiments to implement it into routine clinical diagnostics.

Keywords: FokI; GNAS; SNP; T393C; cancer; progression; rs7121; survival; therapy response.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Chromogranins / genetics*
  • Disease Progression
  • GTP-Binding Protein alpha Subunits, Gs / genetics*
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Polymorphism, Single Nucleotide / genetics
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • Chromogranins
  • GNAS protein, human
  • GTP-Binding Protein alpha Subunits, Gs