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Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
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k-RAS mutations in non-small cell lung cancer patients treated with TKIs among smokers and non-smokers: a

Ai-Gui Jiang1, Hui-Yu Lu1

  • 1Department of Respiratory Diseases, Jiangsu Taizhou People's Hospital, Taizhou City, Jiangsu Province, China P.R.

Contemporary Oncology (Poznan, Poland)
|July 1, 2016
PubMed
Abstract

Insights

Smoking significantly increases the incidence of k-RAS mutations in non-small cell lung cancer (NSCLC) patients undergoing tyrosine-kinase inhibitor (TKI) therapy. This finding suggests smoking may lead to poorer outcomes in NSCLC treated with TKIs.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacology

Background:

  • Epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs) are used in advanced non-small cell lung cancer (NSCLC).
  • K-RAS mutations are implicated in TKI treatment response.
  • The relationship between smoking and k-RAS mutations in NSCLC patients receiving TKIs requires further investigation.

Purpose of the Study:

  • To conduct a meta-analysis assessing the association between smoking history and k-RAS mutations in NSCLC patients treated with TKIs.

Main Methods:

  • A systematic literature search was performed on MEDLINE and Web of Science up to March 15, 2014.
  • Pooled relative risk (RR) was calculated using fixed or random effect models based on heterogeneity.
  • Power analyses were conducted to evaluate study power.

Main Results:

  • The meta-analysis included 12 studies with 1193 patients; 16.4% had k-RAS mutations.
  • The incidence of k-RAS mutations was higher in smokers (22.8%) compared to non-smokers (5.4%), with a pooled RR of 2.991 (p=0.000).
  • Subgroup analysis showed a higher RR in Caucasians (3.336) but not significantly in Asians (2.093) due to underpowered sample size.

Conclusions:

  • Smoking is significantly associated with an increased incidence of k-RAS mutations in NSCLC patients treated with TKIs.
  • This association may contribute to a worse prognosis for smoking NSCLC patients receiving TKI therapy.
  • Further research is needed to clarify the impact of smoking on TKI efficacy in diverse populations.
Keywords:
k-RAS mutationsnon-small cell lung cancersmokingtyrosine-kinase inhibitions

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