We detected the epidermal growth factor receptor L858R, MSH2 R929* and telomerase reverse transcriptase amplification in the lung cancer specimen; CDH1 c.1320+1G>T mutation in the gastric cancer (GC) specimen; and MLH1 c.1896+5G>A germline mutation in the lung and GC specimens by 450 cancer-related gene mutations detection using next-generation sequencing technology.
Our results suggest that a common functional promoter polymorphism, TERTrs2853669, may influence both telomere length and lung cancer risk in the Korean population.
The results of this meta-analysis suggest that the TERTrs2853669 polymorphism is associated with a significantly increased risk of cancer, particularly lung cancer, in Asian populations.
The ectopic overexpression of CPSF4 upregulated the hTERT promoter-driven report gene expression and activated the endogenous hTERT mRNA and protein expression and the telomerase activity in lung cancer cells and normal lung cells.
Our study was powered to identify strong risk loci for lung cancer in African Americans; we confirmed results previously reported in African Americans and other populations for two loci near plausible candidate genes, CHRNA5 and TERT, on 15q25.1 and 5p15.33 respectively, are associated with lung cancer.
The quantity of plasma DNA was determined using quantitative Real-Time PCR with amplification of the human telomerase reverse transcriptase (hTERT) gene in 151 patients that suffer from lung cancer and 79 healthy controls.
The differences in risk level between Israeli Jews and non-Jews could not be explained by lung cancer genetic risk variants which were identified in GWAS (genes in the CHRNA5, TERT and CLPTM1L regions).
The gene-based SKAT-O analysis implicated TERT as the most relevant gene in the 5p15.33 region for adenocarcinoma (P = 7.84×10(-7)) and lung cancer (P = 2.37×10(-5)) risk.
We evaluated the antitumor activity of the Bax gene and green fluorescent protein/tumor necrosis factor-related apoptosis-inducing ligand (GFP/TRAIL) fusion gene driven by the human telomerase reverse transcriptase promoter both separately and combined in the human ovarian cancer lines SKOV3ip and DOV13 and human lung cancer line H1299.
These results indicate that (a) the HBEC model system is a powerful new approach to assess the contribution of individual and combinations of genetic alterations to lung cancer pathogenesis; (b) a combination of four genetic alterations, including human telomerase reverse transcriptase overexpression, bypass of p16/RB and p53 pathways, and mutant K-RAS(V12) or mutant EGFR, is still not sufficient for HBECs to completely transform to cancer; and (c) EGFR tyrosine kinase inhibitors inhibit the growth of preneoplastic HBEC cells, suggesting their potential for chemoprevention.
Our findings, combined with previous studies, suggest that polymorphisms in the TERT gene contribute to the risk for lung cancer in the Chinese Han population.
All three mapped to Chromosome 5 CLPTM1L-TERT region, previously shown to be associated with lung cancer risk in smokers and in never-smoker Asian women, and risk of other cancers including breast, ovarian, colorectal, and prostate.
As a result, 15 SNPs on or near 12 genes and one miRNA with strong evidence of association with lung cancer risk were identified, including TERT (rs2736098), CHRNA3 (rs1051730), AGPHD1 (rs8034191), CLPTM1L (rs401681 and rs402710), BAT3 (rs3117582), TRNAA (rs4324798), ERCC2 (Lys751Gln), miR-146a2 (rs2910164), CYP1B1 (Arg48Gly), GSTM1 (null/present), SOD2 (C47T), IL-10 (-592C/A and -819C/T), and TP53 (intron 6).
These results suggest that genetic variants in the TERT-CLPTM1L gene may predispose individuals to be susceptible to LC, particularly NSCLC, in the Chinese population.
Our data demonstrated that hTERT promoter-driven IFN-beta expression was the tumor-specific, decreased the cell viability of tumor cells but not normal cells, and induced tumor cell apoptosis via activation of caspase pathway and release of cytochrome c. AAV-mediated IFN-beta expression driven by hTERT promoter significantly suppressed the growth of colorectal cancer and lung cancer xenograft in mice and resulted in tumor cells death in vivo.
The long TL genetic score was significantly associated with increased risk of lung adenocarcinoma (P = 6.3 × 10(-15)), even after exclusion of a SNP residing in a known lung cancer susceptibility region (TERT-CLPTM1L) P = 6.6 × 10(-6)).
Case-Control Study on Impact of the Telomerase Reverse Transcriptase Gene Polymorphism and Additional Single Nucleotide Polymorphism (SNP)- SNP Interaction on Non-Small Cell Lung Cancers Risk in Chinese Han Population.
We verified the tumor-specific binding activity of AP-2beta for the hTERT promoter in vitro and in vivo and detected high expression levels of AP-2beta in lung cancer cells.
This study examined associations between five single nucleotide polymorphisms (SNPs) of TERT-CLPTM1L (rs402710, rs401681, rs465498, rs4975616, and rs2736100) and lung cancer in a Chinese Han population in the Hubei Province.
However, the joint effect of TERT and CLPTM1L variants increased the risk of lung cancer, especially squamous cell carcinoma, with an adjusted OR of 3.274.
We then found that GRSs used as instrumental variables to predict longer telomere length were associated with increased lung cancer risk (OR = 1.51 (95% CI = 1.34-1.69) for upper vs. lower quartile of the weighted GRS, p value = 4.54 × 10(-14) ) even after removing rs2736100 (p value = 4.81 × 10(-3) ), a SNP in the TERT locus robustly associated with lung cancer risk in prior association studies.