STAT3 rs4796793 contributes to lung cancer risk and clinical outcomes of platinum-based chemotherapy

Int J Clin Oncol. 2019 May;24(5):476-484. doi: 10.1007/s10147-018-01386-7. Epub 2019 Jan 28.

Abstract

Background: Signal transducer and activator of transcription (STAT) 3 plays a vital role in carcinogenesis and drug response. Platinum-based chemotherapy is the first-line treatment for lung cancer patients, especially those in advanced stages. In the present study, we investigated the association of STAT3 polymorphism rs4796793 with lung cancer susceptibility, platinum-based chemotherapy response, and toxicity.

Methods: A total of 498 lung cancer patients and 213 healthy controls were enrolled in the study. 467 of them received at least 2-cycle platinum-based chemotherapy. Unconditional logistical regression analysis was used to assess the associations.

Results: STAT3 rs4769793 G allele carriers had an increased susceptibility of lung cancer [additive model: adjusted OR (95% CI) 1.376 (1.058-1.789), P = 0.017; recessive model: adjusted OR (95% CI) 1.734 (1.007-2.985), P = 0.047]. Rs4769793 was not significantly associated with platinum-based chemotherapy response in lung cancer patients. STAT3 rs4796793 was associated with an increased risk of severe overall toxicity [additive model: adjusted OR (95% CI) 1.410 (1.076-1.850), P = 0.013; dominant model: adjusted OR (95% CI) 1.638 (1.091-2.459), P = 0.017], especially hematological toxicity [additive model: adjusted OR (95% CI) 1.352 (1.001-1.826), P = 0.049].

Conclusions: STAT3 rs4796793 may be considered as a potential candidate biomarker for the prediction of susceptibility and prognosis in Chinese lung cancer patients. However, well-designed studies with larger sample sizes are required to verify the results.

Keywords: Lung cancer; Platinum-based chemotherapy; Prognosis; STAT3 rs4769793; Susceptibility.

Publication types

  • Meta-Analysis

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Asian People / genetics
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Platinum / pharmacology
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • STAT3 Transcription Factor
  • Treatment Outcome

Substances

  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Platinum