Relationship between MAPK1 gene polymorphism and gefitinib hepatotoxicity in NSCLC patients with activating EGFR mutations / 药学学报

ABSTRACT

The hepatotoxicity of gefitinib is an important factor limiting its clinical application. In order to control the toxicity, we conducted this study to find the gene variation that can explain and predict the occurrence and severity of hepatotoxicity of gefitinib. Ninety patients with non-small cell lung cancer were included in the retrospective clinical study. Detailed hepatotoxicity induced by gefitinib and epidemiological characteristics were recorded. Twenty-six candidate single-nucleotide polymorphisms of molecular targets, metabolic enzymes, transporters and chemokines were genotyped by matrix-assisted laser desorption/ionization time-of-flight platform. Various confounding factors, such as age, gender and smoking status, were included in the follow-up analysis and variability in the extent of hepatotoxicity was best explained by a multivariate logistic regression model incorporating. The severity of hepatotoxicity was associated with mitogen-activated protein kinase 1 rs13515 (OR=9.467, P=0.074). The research about pharmacogenomic of gefitinib identified the determinants of the drug-induced liver injury. These findings provide a basis to design clinical trials targeting a particular toxicity of gefitinib or similarly targeted agents to benefit patients on long-term gefitinib treatment.