Rho GTPases: RAC1 polymorphisms affected platinum-based chemotherapy toxicity in lung cancer patients

Cancer Chemother Pharmacol. 2016 Aug;78(2):249-58. doi: 10.1007/s00280-016-3072-0. Epub 2016 Jun 14.

Abstract

Purpose: Lung cancer is the leading cause of cancer deaths in the world. The toxicity of platinum-based chemotherapy is a main reason limiting its clinical effects. RAC1, as a member of the Rho family of small guanosine triphosphatases (GTPases), was reported to be related to most cancers, such as breast cancer, gastric cancer, testicular germ cell cancer, and lung cancer. Its potential of becoming a drug target in cancer treatment has been investigated in recent years. The aim of this study was to investigate the association between genetic polymorphisms and platinum-based chemotherapy toxicity.

Methods: We enrolled 317 lung cancer patients randomly. Nineteen polymorphisms of HSP genes and Rho family genes were genotyped by Sequenom MassARRAY. The logistic regression was performed by PLINK to compare the relevance of polymorphisms and toxicity outcome.

Results: We found that the polymorphisms of RAC1 rs836554, rs4720672, and rs12536544 were significantly associated with platinum-based chemotherapy toxicity (p = 0.018, p = 0.044, and p = 0.021, respectively).

Conclusions: RAC1 rs836554, rs4720672, and rs12536544 polymorphisms may be novel and useful genetic markers to predict the toxicity induced by platinum-based chemotherapy in lung cancer patients.

Keywords: Genetic polymorphism; Lung cancer; Platinum-based chemotherapy; RAC1; Toxicity.

Publication types

  • Clinical Trial

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Female
  • Genotype
  • Heat-Shock Proteins / genetics*
  • Humans
  • Logistic Models
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Platinum Compounds / administration & dosage
  • Polymorphism, Single Nucleotide
  • rac1 GTP-Binding Protein / genetics*

Substances

  • Heat-Shock Proteins
  • Platinum Compounds
  • RAC1 protein, human
  • rac1 GTP-Binding Protein