By chromosome conformation capture, it was identified that the segment containing these two SNPs could interact with TERT (telomerase reverse transcriptase) promoter, thus indicating that these SNPs confer lung cancer risk by regulating TERT expression instead of CLPTM1L.
After the 2nd stage validation (975 cases versus 1022 controls), the study clarified the association that rs2736100 of the TERT gene conferred the highest significant risk of lung cancer (P=4×10(-3) in the 1st stage association, P=4×10(-4) in the 2nd stage validation, and P=1×10(-5), odds ratio=1.24 in the combined population).
We constructed a recombinant adenovirus containing the human sodium iodide symporter (hNIS) gene directed by the hTERT promoter, characterized the ability of infected cells in uptaking iodide, and explored the therapeutic efficacy of (131)I in a lung cancer cell line in vitro.
Two glioma risk variants, TERTrs2853676 and CDKN2BAS1 rs4977756, which are located in regions previously associated with lung cancer, were associated with increased risk of adenocarcinoma (OR = 1.16; 95% CI = 1.10 to 1.22; P = 1.1×10(-8)) and squamous cell carcinoma (OR = 1.13; CI = 1.07 to 1.19; P = 2.5×10(-5)), respectively.
Genetic factors included six variants implicated in a previous a genome-wide association study (GWAS) of NPC and three variants residing near the CHRNA3 and TERT genes that were linked to lung cancer risk in Asian populations.
Recently, a number of case-control studies have been carried out to investigate the relationship between the rs2736100 polymorphism in TERT and genetic susceptibility to lung cancer.
We identified one novel variant at the level corrected for multiple comparisons (rs2741354 in EPHX2 at 8p21.1 with p value = 7.4 × 10(-6)), and confirmed the associations between TERT (rs2736100) and the HLA region and lung cancer risk.
We termed this lung cancer system TTS (TTF1 gene under the control of human telomerase reverse transcriptase promoter and human surfactant protein A1 promoter).
These data demonstrate a potential association between the TERT-CLPTM1L variant and levels of bulky DNA adducts measured by (32)P-postlabeling and hence a basis for susceptibility to the development of lung cancer.
A common genetic variant, telomerase reverse transcriptase (TERT) rs2736098, was recently reported to be associated with lung cancer risk in Caucasians.
In the subgroup analysis based on cancer type, the TERTrs2736098 with the A allele was 1.299 times more frequent than that with the G allele (OR = 1.299, 95% CI = 1.216-1.386) under the allelic genetic model in lung cancer, and 1.152 times (OR = 1.152, 95% CI = 1.032-1.286) that in bladder cancer.
In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma.
Longer telomere length in peripheral white blood cells is associated with risk of lung cancer and the rs2736100 (CLPTM1L-TERT) polymorphism in a prospective cohort study among women in China.
Single-nucleotide polymorphisms rs421629 on 5p15.33 and rs1948, rs660652, rs8040868 and rs2036527 on 15q25.1, previously identified as lung cancer risk or nicotine-addiction modifiers, were associated with tumor DNA methylation levels in the promoters of TERT and CHRNB4 (P<0.001), respectively, in two independent sample sets (n=82; n=150).
These results indication that pure and impure diosgenin prevents telomerase activity by down regulation of the hTERT gene expression in A549 lung cancer cell line, with the difference that pure compound is more effective than another.
Human telomerase reverse transcriptase (hTERT) gene amplification was detected in pleural effusions of patients with lung cancer (n = 69) and in patients with benign lung disease (n = 46) when using a quantitative polymerase chain reaction (qPCR) technique.