Abstract
BACKGROUND: Lung cancer is a leading cause of cancer-related deaths globally. While single-nucleotide polymorphisms (SNPs) are established genetic modulators of cancer susceptibility, the specific functions of SNPs in the mammalian target of rapamycin (mTOR) pathway in lung cancer pathogenesis remain largely unclear. This study investigated the associations between a specific SNP in the promoter region of the mTOR gene, the corresponding mTOR protein expression levels, and lung cancer susceptibility in the study population. METHODS: Genotyping of 136 healthy controls and 241 lung cancer patients was performed using SNP scanning high-throughput technology. Lung cancer patients were further classified into lung squamous cell carcinoma (LUSC), lung adenocarcinoma (LUAD), and small cell lung cancer (SCLC). Logistic regression, independent samples t-test, and Chi-squared test were used for susceptibility and difference analysis. Protein expression differences were analyzed using the Clinical Proteomics Tumor Analysis Consortium (CPTAC) database and immunohistochemistry (IHC). RESULTS: The results showed that mTOR-rs2295080 was significantly associated with the risk of developing LUAD and SCLC. The GT genotype reduced the risk of LUAD compared with the TT genotype [odds ratio (OR) =0.513; 95% confidence interval (CI): 0.300-0.877; P=0.02]. The G allele reduced the risk of SCLC compared to the T allele (OR =0.377; 95% CI: 0.185-0.769; P=0.007). IHC results according to genotype and pathology type showed that rs2295080-GT had the lowest protein expression levels of MTOR in tumor tissues of LUAD and LUSC patients compared to those of GG and TT. CONCLUSIONS: The mTOR rs2295080 polymorphism is associated with a reduced risk of lung cancer and may exert a protective effect by reducing protein expression.