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Effects of single-nucleotide polymorphisms in the mTORC1 pathway on the risk of brain metastasis in patients with non-small cell lung cancer

Effects of single-nucleotide polymorphisms in the mTORC1 pathway on the risk of brain metastasis in patients with non-small cell lung cancer

Authors :
Jiankun Zheng
Yi Huang
Yiquan Xu
Yunan Zhao
Lihong Weng
Hongru Li
Yina Huang
Ying Lin
Yusheng Chen
Source :
Journal of Cancer Research and Clinical Oncology
Publication Year :
2019
Publisher :
Springer Science and Business Media LLC, 2019.

Abstract

Purpose The mammalian target of rapamycin complex 1 (mTORC1) signaling pathway plays a vital role in cancer development and progression. This study aimed to investigate the relationship between genotype variants in mTORC1 pathway and the risk of brain metastasis (BM) in patients with non-small cell lung cancer (NSCLC). Methods We extracted genomic DNA from blood samples of 501 NSCLC patients and genotyped eight single-nucleotide polymorphisms (SNPs) in three core genes [mammalian target of rapamycin (mTOR), mammalian lethal with sec-13 protein 8 (mLST8) and regulatory-associated protein of mTOR (RPTOR)] of the mTORC1 pathway. The associations between these SNPs and the risk of BM development were assessed. Results The AG/GG genotype of mLST8:rs26865 and TC/CC genotype of mLST8:rs3160 were associated with an increased risk of BM [hazard ratios (HR) 2.938, 95% confidence interval (CI) 1.664–5.189, p p p 2), high level of squamous cell carcinoma (SCC) antigen and Ki-67 proliferation index. Moreover, patients with AG/GG genotype of mLST8:rs26865 had significantly lower median overall survival than those with AA genotype (12.1 months versus 21.6 months, p = 0.04). Conclusions Our results indicate that polymorphisms in mTORC1 pathway were significantly associated with increased risk of BM and may be valuable biomarkers to identify NSCLC patients with a high risk of BM.

Details

ISSN :
14321335 and 01715216
Volume :
146
Database :
OpenAIRE
Journal :
Journal of Cancer Research and Clinical Oncology
Accession number :
edsair.doi.dedup.....8ae48ae68897abd4c8f844c5a9ca7045
Full Text :
https://doi.org/10.1007/s00432-019-03059-y