STAT6 polymorphism was correlated with gefitinib-induced diarrhea in patients with non-small cell lung cancer.

Abstract

e21046 Background: Gefitinib-induced diarrhea can be severe, if not properly handled, and can result in severe dose reductions and treatment interruptions or discontinuation. However, the mechanism of gefitinib-induced diarrhea remains unclear. STAT6 promotes disruption of epithelial tight junction integrity, intestinal inflammation and allergic disorders in intestine. Therefore, we explored the correlation between variations in STAT6 and gefitinib-induced diarrhea in advanced non-small cell lung cancer (NSCLC) patients. Methods: A total of 160 advanced NSCLC patients carrying EGFR mutations were enrolled. 8 tag single nucleotide polymorphisms (SNP) in STAT6, including rs10876963, rs167769, rs3122929, rs3024975, rs841718, rs324013, rs324015 and rs703817, were selected by Heploview 4.2 and sequenced by Agena MassARRAY System. The associations between tag SNPs of STAT6 and diarrhea were analyzed by Chi square test and multivariate logistic regression. This study was approved by the ethical committee of Sun Yat-Sen University Cancer Center. Results: 71 patients (44.4%) suffered at least grade 1 gefitinib-induced diarrhea. We found rs167769 was associated with gefitinib- induced diarrhea in NSCLC patients. STAT6 rs167769 TT carriers were all suffering from gefitinib-induced diarrhea (OR = 2.4*1010, p = 0.999). Patients with STAT6 rs167769 TT have higher risk of developing severe (grade ≥ 2) diarrhea than those with STAT6 rs167769 CC/CT. Conclusions: STAT6 rs167769 is a predictive biomarker for gefitinib-induced diarrhea and the analysis of polymorphisms of STAT6 rs167769 might be beneficial to optimize gefitinib treatment. Further studies are needed to clarify the underlying mechanisms. Clinical trial information: NCT01994057.