STAT3 and STAT6 polymorphisms predict the severity of adverse reactions in Chinese NSCLC patients receiving EGFR-TKIs therapy

Abstract

A total of 162 non-small cell lung cancer (NSCLC) patients were divided into discovery (N = 68) and validation (N = 94) groups. Nine Janus kinase/Signal transducer and activator of transcription (JAK/STAT) pathway-related single nucleotide polymorphisms were selected to explore the potential associations between genetic polymorphisms and adverse drug reactions (ADRs). The TT genotype of STAT6 rs324011 was significantly associated with severe ADRs in the recessive genetic model (TT vs. CC + CT, OR = 13.5, 95% CI = 2.12–86.09, p = 0.006 in the discovery group; OR = 8.41, 95% CI = 1.95–36.19, p = 0.004 in the validation group). The T allele was associated with a higher incidence of severe ADRs than was the C allele of rs324011 (OR = 3.67, 95% CI = 1.46–9.19, p = 0.006 in the discovery group; OR = 3.17, 95% CI = 1.44–6.99, p = 0.004 in the validation group). Patients with the CC genotype in STAT3 rs1053023 (and rs1053005) or the TT genotype of STAT6 rs324011 were likely to experience severe epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) related ADRs.

Graphical abstract

A graphical illustration of this study was shown in the Graphical Abstract. The current study process of nine critical SNPs involving the JAK/STAT pathway in Chinese NSCLC participants receiving EGFR-TKIs therapy was illustrated.

Keywords:

• Single nucleotide polymorphisms
• JAK/STAT signalling pathway
• non-small cell lung cancer
• ADRs
• first-generation or second-generation EGFR-TKI
• STAT

Acknowledgement

We thank the help of everybody in the study.

Data availability statement

The data used in this study are not publicly available due to the privacy of the study participants but are available from the corresponding author upon reasonable request.

Disclosure statement

No potential conflict of interest was reported by the authors.

Ethics approval and consent to participate

The Huashan Hospital Ethics Committee approved this study (No. 2017-011), which was conducted according to the Helsinki Declaration. All patients provided their written consent.

Additional information

Funding

The work was supported by the National Natural Science Foundation of China to QL (81973399) and to TW (81901399), the Shanghai ‘Rising Stars of Medical Talent’ Youth Development Program to QL (Youth Medical Talents-Clinical Pharmacist Program), Shanghai Key Clinical Specialty Projects-Clinical Pharmacy to MZ (shslczdzk06502), Clinical pharmacy management committee of Shanghai Hospital Association to XS (YS2021015).