Gefitinib is a widely used targeted therapeutic drug in East Asian non-small cell lung cancer (NSCLC) patients. This research retrospectively investigated the relationship between the polymorphisms of genes involved in NF-κB pathways and gefitinib-related Adverse Drug Reactions (ADRs). From 2011 to 2016, 109 NSCLC patients were enrolled in this study. Thirty-two SNPs of 15 genes were genotyped with a Sequenom MassARRAY system. We collected 34 paired RNA samples before and after gefitinib administration for the detection of whole blood RNA expression of genes in NF-κB pathways (NFKBIA, NFKB1, NFKB2, RELA, RELB, and TNFAIP3). IKBKB rs2272733 (CC vs non-CC: OR = 0.256, 95% CI 0.087–0.753, P = 0.013) and IKBKE rs12142086 (CC vs non-CC: OR = 3.640, 95% CI 1.320–10.039, P = 0.013) were significantly associated with gefitinib-induced skin toxicity. IKBKE rs2151222 was associated with diarrhea with the odds ratio of non-TT vs TT as 0.162 (non-TT vs TT: 95% CI 0.034–0.775, P = 0.023). Furthermore, RELA rs11227247 was a predictor for hepatic toxicity (GG vs non-GG: OR = 0.212, 95% CI 0.062–0.726, P = 0.013). None of the gene expression levels after drug administration were determined to be significant predictors for adverse drug reactions by a logistics regression analysis. Polymorphisms of IKBKB, IKBKE, and RELA are potential biomarkers for predicting gefitinib-related ADRs. Further studies are needed to understand the underlying mechanisms for diagnostic and prophylactic therapy applications.

吉非替尼是在东亚非小细胞肺癌（NSCLC）患者中广泛使用的靶向治疗药物。这项研究回顾性研究了涉及NF-κB通路的基因多态性与吉非替尼相关的药物不良反应（ADR）之间的关系。从2011年到2016年，本研究招募了109名非小细胞肺癌患者。用Sequenom MassARRAY系统对15个基因的32个SNP进行基因分型。我们在吉非替尼给药前后收集了34对配对的RNA样本，用于检测NF-κB通路中的全血RNA表达基因（NFKBIA，NFKB1，NFKB2，RELA，RELB和TNFAIP3）。IKBKB rs2272733（CC与非CC：OR = 0.256，95％CI 0.087–0.753，P = 0.013）和IKBKE rs12142086（CC与非CC：OR = 3.640，95％CI 1.320-10.039，P  = 0.013）与吉非替尼诱导的皮肤毒性显着相关。IKBKE rs2151222与腹泻有关，非TT与TT的比值比为0.162（非TT与TT：95％CI 0.034-0.775，P  = 0.023）。此外，RELA rs11227247是肝毒性的预测指标（GG与非GG：OR = 0.212，95％CI 0.062-0.726，P  = 0.013）。通过后勤回归分析，给药后的基因表达水平均未确定为药物不良反应的重要预测因子。IKBKB，IKBKE和RELA的多态性是预测吉非替尼相关ADR的潜在生物标志物。需要进一步的研究来了解诊断和预防疗法应用的潜在机制。