Side effects of tyrosine kinase inhibitors therapy in patients with non‑small cell lung cancer and associations with <em>EGFR</em> polymorphisms: A systematic review and meta‑analysis

Obradovic,Jasmina; Todosijevic,Jovana; Jurisic,Vladimir

doi:10.3892/ol.2022.13649

February-2023 Volume 25 Issue 2

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February-2023 Volume 25 Issue 2

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Article

Side effects of tyrosine kinase inhibitors therapy in patients with non‑small cell lung cancer and associations with EGFR polymorphisms: A systematic review and meta‑analysis

Authors:
- Jasmina Obradovic
- Jovana Todosijevic
- Vladimir Jurisic
View Affiliations / Copyright

Affiliations: Department of Sciences, Institute for Information Technologies, University of Kragujevac, 34000 Kragujevac, Republic of Serbia, Institute of Biology and Ecology, Faculty of Sciences, University of Kragujevac, 34000 Kragujevac, Republic of Serbia, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Republic of Serbia
Article Number: 62
|
Published online on: December 23, 2022

https://doi.org/10.3892/ol.2022.13649
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Abstract

Rash and diarrhea are common side effects of tyrosine kinase inhibitor (TKI) therapy administered to patients with non‑small cell lung cancer (NSCLC). The polymorphisms of the epidermal growth factor receptor (EGFR) gene may be a potential predictor of these side effects. The aim of the present meta‑analysis was to examine the association of EGFR polymorphisms and TKI‑associated toxicities. Electronic databases (PubMed, Scopus and ISI Web of Science) were searched for relevant studies. According to the inclusion and exclusion criteria, a search of the databases identified 4,918 results, among which 6 clinical trials were obtained with 1,318 patients with NSCLC. A total of 9 EGFR single nucleotide polymorphisms (SNPs) associated with TKI toxicity were identified including, rs11568315, rs712829, rs712830, rs2227983, rs2075102, rs2293347, rs11977388, rs4947492 and rs884225. The data associated with skin toxicity from rs11568315, rs712829 and rs712830 were analyzed in the present meta‑analysis. Data from rs11568315 were also analyzed in relation to diarrhea. Among all the examined SNPs, statistically significant results were obtained under the dominant genetic model for CA repeats in rs11568315 (SS vs. SL+LL) with skin toxicity. The long CA repeat (SL+LL) carriers were more likely to experience skin toxicity associated with TKIs (P=0.005). By contrast, there was no significant result for diarrhea (P=0.661) under dominant genetic model for CA repeats.

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