Genetic variations of rs6928 and rs5999521 of ERK2 were found to have correlation with the risk of brain metastasis in patients with lung adenocarcinoma.

Abstract

BackgroundPatients with lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutations have a high risk of brain metastasis (BM). Mitogen-activated protein kinase (MAPK) is an important mediator of EGFR/c-MET crosstalk, which is involved in development of BM in non-small cell lung cancer. Here, we investigated the association of MAPK genetic variations with the risk of BM in patients with lung adenocarcinoma.MethodsPatients with pathologically confirmed lung adenocarcinoma from two Hospitals (n=120, discovery cohort; n=213, validation cohort) were enrolled. Magnetic resonance imaging (MRI) was employed for BM follow-up after the completion of planned therapy. Single nucleotide polymorphisms (SNPs) of MAPK pathway genes were tested with blood samples.ResultsAfter adjustment for sex, age, staging, smoking status, surgery, and thoracic radiotherapy, extracellular signal-regulated kinase 2 (ERK2) rs6928 and rs5999521 SNPs were found to be associated with increased risk of BM. The rs6928 GG and CG genotypes were associated with 2.033-fold (P=0.033) and 1.910-fold (P=0.012) increases in the risk of developing BM compared with the CC genotype. For rs5999521, the risk of developing BM was increased by 1.993-fold (P=0.037) in patients with the GG genotype and 1.834-fold (P=0.019) in patients with the AG genotype compared with patients with the AA genotype. Furthermore, patients with genotypes of higher risk of BM showed higher EGFR mutation rates and tended to have >1 BM lesions.ConclusionsIn patients with lung adenocarcinoma, ERK2 rs6928 and rs5999521 SNPs contributed to BM risk, particularly in patients with specific genotypes.