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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
- 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.
- Subjects :
- Risk
Adult
Male
Oncology
Cancer Research
medicine.medical_specialty
Lung Neoplasms
Genotype
Proliferation index
Original Article – Clinical Oncology
Single-nucleotide polymorphism
Mechanistic Target of Rapamycin Complex 1
Genetic polymorphisms
Polymorphism, Single Nucleotide
Carcinoma, Non-Small-Cell Lung
Internal medicine
medicine
Humans
Genetic Predisposition to Disease
Lung cancer
mTORC1
PI3K/AKT/mTOR pathway
Aged
Retrospective Studies
Aged, 80 and over
Hematology
Brain Neoplasms
business.industry
Brain metastasis
RPTOR
Biomarker
DNA, Neoplasm
General Medicine
Middle Aged
medicine.disease
Mutation
Female
business
Signal Transduction
Subjects
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