Telomerase Reverse Transcriptase Rs2736100 Research Articles

Association of TERT (rs2736098 and rs2736100) genetic variants with elevated risk of hepatocellular carcinoma: a retrospective case–control study

Hepatocellular carcinoma (HCC) is an inflammatory problematic issue with higher mortality among different ethnic populations. The telomerase reverse transcriptase (TERT) gene has an imperative role in the proliferation of various cancerous illnesses, particularly HCC. Moreover, the TERT (rs2736098 and rs2739100) variants were correlated with the HCC susceptibility and telomere shortening, but with unconvincing outcomes. The main purpose of this outward work is to assess the correlation between these significant variants within the TERT gene and the elevated risk of HCC with the aid of various computational bioinformatics tools. This study included 233 participants [125 cancer-free controls and 108 HCC patients] from the same locality. In addition, 81.5% of HCC patients were positive for HCV autoantibodies, while 73.1% of HCC patients were positive for cirrhotic liver. Genomic DNA of the TERT (rs2736098 and rs2736100) variants were characterized utilizing the PCR–RFLP method. Interestingly, the frequencies of TERT (rs2736098*A allele) and TERT (rs2736100*T allele) conferred a significant correlation with increased risk of HCC compared to healthy controls (p-value = 0.002, and 0.016, respectively). The TERT (rs2736098*A/A) genotype indicated a definite association with positive smoking and splenomegaly (p-value < 0.05), while the TERT (rs2736100*T/T) genotype observed a significant difference with higher levels of HCV autoantibodies (p-value = 0.009). In conclusion, this significant work confirmed the contribution of the TERT (rs2736098*A and rs2736100*T) alleles with elevated risk of HCC progression and telomere shortening among Egyptian subjects.

Ethnicity-specific association between TERT rs2736100 (A > C) polymorphism and lung cancer risk: a comprehensive meta-analysis

The rs2736100 (A > C) polymorphism of the second intron of Telomerase reverse transcriptase (TERT) has been confirmed to be closely associated with the risk of Lung cancer (LC), but there is still no unified conclusion on the results of its association with LC. This study included Genome-wide association studies (GWAS) and case–control studies reported so far on this association between TERT rs2736100 polymorphism and LC to clarify such a correlation with LC and the differences in it between different ethnicities and different types of LC. Relevant literatures published before May 7, 2022 on ‘TERT rs2736100 polymorphism and LC susceptibility’ in PubMed, EMbase, CENTRAL, MEDLINE databases were searched through the Internet, and data were extracted. Statistical analysis of data was performed in Revman5.3 software, including drawing forest diagrams, drawing funnel diagrams and so on. Sensitivity and publication bias analysis were performed in Stata 12.0 software. The C allele of TERT rs2736100 was associated with the risk of LC (Overall population: [OR] = 1.21, 95%CI [1.17, 1.25]; Caucasians: [OR] = 1.11, 95%CI [1.06, 1.17]; Asians: [OR] = 1.26, 95%CI [1.21, 1.30]), and Asians had a higher risk of LC than Caucasians (C vs. A: Caucasians: [OR] = 1.11 /Asians: [OR]) = 1.26). The other gene models also showed similar results. The results of stratified analysis of LC patients showed that the C allele was associated with the risk of Non-small-cell lung carcinoma (NSCLC) and Lung adenocarcinoma (LUAD), and the risk of NSCLC and LUAD in Asians was higher than that in Caucasians. The C allele was associated with the risk of Lung squamous cell carcinoma (LUSC) and Small cell lung carcinoma(SCLC) in Asians but not in Caucasians. NSCLC patients ([OR] = 1.27) had a stronger correlation than SCLC patients ([OR] = 1.03), and LUAD patients ([OR] = 1.32) had a stronger correlation than LUSC patients ([OR] = 1.09).In addition, the C allele of TERT rs2736100 was associated with the risk of LC, NSCLC and LUAD in both smoking groups and non-smoking groups, and the risk of LC in non-smokers of different ethnic groups was higher than that in smokers. In the Asians, non-smoking women were more at risk of developing LUAD. The C allele of TERT rs2736100 is a risk factor for LC, NSCLC, and LUAD in different ethnic groups, and the Asian population is at a more common risk. The C allele is a risk factor for LUSC and SCLC in Asians but not in Caucasians. And smoking is not the most critical factor that causes variation in TERT rs2736100 to increase the risk of most LC (NSCLC, LUAD). Therefore, LC is a multi-etiological disease caused by a combination of genetic, environmental and lifestyle factors.

Analysis of TERT Rs2736100 genotype distribution in laryngeal squamous cell carcinoma patients.

The applicability of the telomerase reverse transcriptase (TERT) gene Rs2736100 polymorphism in cancer research has been well documented for various malignancies except for head and neck cancers, where data is sparse. This study aimed to analyze this polymorphism with the pathological characterizers of laryngeal squamous cell carcinoma (LSCC) patients. Genetic testing was performed using the Real-time PCR technique on 56 paired samples of biological material (blood and tissue). Data were analyzed using Epi info 7 software. The subjects were predominantly male (95% vs. 5%), with a median age of 62 years, and smokers (89%). The primary tumor origin site was the glottic region (34%), and the advanced clinical stages III-IV were more common (46% vs. 18%). Results show high frequencies for the mutated variants of Rs2736100 (CC 36%>AC 34%>AA 30%), while distribution according to tumor classification criteria leaned towards moderately differentiated carcinoma specimens in T3-T4 stages for the AC/CC variants (P-value without statistical significance) but positively favored the relationship between the AA variant and lack of lymph node metastasis (P=0.0106). The genotypes tend to associate themselves with a better histological presentation regarding the pattern of tumor invasion and, thus, better prognostic values for LSCC. Results suggest that the wild-type genotype of TERT Rs2736100 may be a protective factor for lymph node metastasis and histological pattern of tumor invasion in LSCC. Results regarding the synergistic relationship between cancer and smoking corroborate literature data for moderate to severe smokers regardless of the genetic variant.

Assessment of Telomerase Reverse Transcriptase Single Nucleotide Polymorphism in Sleep Bruxism.

Introduction: Sleep bruxism (SB) is a widespread masticatory muscle activity during sleep and affects approximately 13.2% of the general population. Telomerase reverse transcriptase (TERT) plays a role in preventing the shortening of the telomere. This prospective, observational study aimed to investigate the relationship between single nucleotide polymorphism (SNP) of TERT and the severity of SB and to identify the independent risk factors for SB. Methods: A total of 112 patients were diagnosed by performing one-night polysomnography based on the guidelines of the American Academy of Sleep Medicine. TERT SNP was detected by real-time quantitative polymerase chain reaction (qPCR). Results: Statistical analysis showed the lack of relationship between the rs2853669 polymorphism of TERT and severity of SB (p > 0.05). However, the study showed that patients with allele T in the 2736100 polymorphism of TERT had a lower score on the phasic bruxism episode index (BEI). Based on the receiver operating characteristic (ROC) curve, the value of phasic BEI was 0.8 for the differential prediction for the presence of allele T in the locus. The sensitivity and specificity were 0.328 and 0.893, respectively. The regression analysis showed that lack of TERT rs2736100 T allele, male gender, and arterial hypertension are the risk factors for the higher value of phasic BEI. Conclusion: The SNP of the TERT gene affects phasic SB intensity. The absence of TERT rs2736100 T allele, male sex, and arterial hypertension are independent risk factors for phasic SB.

TERT Gene rs2736100 and rs2736098 Polymorphisms are Associated with Increased Cancer Risk: A Meta-Analysis.

Abnormal telomerase activity plays a key role in the development of carcinogenesis. The variants rs2736100 and rs2736098 of the telomerase reverse transcriptase (TERT) gene, which encodes the telomerase catalytic subunit, are associated with the risk of different types of cancers. However, the results remain controversy. We conducted a meta-analysis to more precisely assess this association. We comprehensively searched the PubMed and Web of Science databases up to June 1, 2020, and retrieved a total of 103 studies in 82 articles, including 89,320 cases and 121,654 controls. Among these studies, 69 published studies including 75,274 cases and 10,3248 controls were focused on rs2736100, and 34 published studies including 14,046 cases and 18,362 controls were focused on rs2736098. The results showed a strong association between variant rs2736100 and cancer risk in all populations. (G vs. T: OR 1.18, 95% CI 1.12-1.24; TG+GG vs. TT: OR 1.23, 95% CI 1.15-1.31; GG vs. TG+TT: OR 1.25, 95% CI 1.16-1.36); the variant rs2736098 was associated with cancer risk in all populations as well (A vs. G: OR 1.13, 95% CI 1.05-1.22; GA+AA vs. GG: OR 1.15, 95% CI 1.04-1.27; AA vs. GA+GG: OR 1.22, 95% CI 1.10-1.38). Stratified analysis based on the cancer type indicated that rs2736100 was associated with an increased risk of thyroid cancer, bladder cancer, lung cancer, glioma, and myeloproliferative neoplasms. rs2736098 only increased the risk of bladder cancer and lung cancer. Moreover, the TERT variants rs2736100 and rs2736098 were associated with a decreased risk of breast cancer and colorectal cancer. The variants rs2736098 and rs2736100 located in 5p15.33 around TERT were associated with increased cancer risk in all populations. These two variants had bidirectional effects in different tumors.

The Association of Aging-Related Polymorphisms with Susceptibility to Lung Cancer: A Case-Control Study in a Japanese Population.

Background:Telomere length is associated with cancer as well as aging. Telomerase reverse transcriptase (TERT), telomere RNA component (TERC) and oligonucleotide/oligosaccharide-binding fold containing 1 (OBFC1) are known to be involved in telomere length regulation. The tumor suppressor p53 (TP53), which has been shown to interact with tumor protein p53-binding protein 1 (TP53BP1), is implicated in the response to telomere shortening and aging. Polymorphisms in the TP53 and TP53BP1 genes are associated with various types of cancer. The aim of this study is to evaluate the impact of aging-related polymorphisms on lung cancer risk. Materials and Methods:This case-control study consists of 462 lung cancer cases and 379 controls from Japan. We examined the effect of TERT rs2736100, TERC rs1881984, OBFC1 rs11191865, TP53 rs1042522 and TP53BP1 rs560191 on the risk of lung cancer using a Taq-Man real-time PCR assay. Unconditional logistic regression was used to assess the adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results: None of the main effects of any of the telomere-related polymorphisms were related to the risk of lung cancer. Similarly, none of the interactive effects of any of the telomere-related polymorphisms with smoking were associated with lung cancer risk. The significant multiplicative interaction between TERT rs2736100 and TP53BP1 rs560191 was statistically significant (OR for interaction = 0.34, 95% CI = 0.14–0.84). The multiplicative interaction between OBFC1 rs11191865 and TP53BP1 rs560191 was also statistically significant (OR for interaction = 2.44, 95% CI = 1.02–5.87) but the OR for interaction was in the opposite direction. Conclusions:Our findings indicate that TP53BP1 rs560191 may predispose to lung cancer risk depending on the genotypes of telomere-related polymorphisms. Additional studies are warranted to confirm the findings suggested in the present study.

Association between the rs2736100 polymorphisms of telomerase reverse transcriptase gene and digestive cancers: A meta-analysis.

The conclusions on the association between the rs2736100 polymorphisms of telomerase reverse transcriptase (TERT) gene polymorphism and digestive cancers risk are still debated. This meta-analysis was conducted to update the association between the TERT rs2736100 polymorphisms and the risk of digestive cancers. The association investigations were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using the meta-analysis method. Eight case-control studies were included in this meta-analysis for associating TERT rs2736100 gene polymorphism and digestive cancer susceptibility. Pooled odds ratio with 95% confidence interval was calculated using a fixed or random-effects model. Overall, no evidence has shown that the TERT rs2736100 polymorphism was associated with the susceptibility to digestive cancers. Besides, stratified analysis with ethnicity also indicated no significant association between TRET rs2736100 and the risk of digestive cancers under all genetic models in both Asian and Caucasian populations were observed. According to the meta-analysis, TERT rs2736100 polymorphism might be unrelated to digestive cancer susceptibility. Evidence with adequate sample size is still needed.

Telomerase reverse transcriptase rs2736098 polymorphism is associated with lung cancer: A meta-analysis.

BackgroundA meta-analysis was conducted to determine whether telomerase reverse transcriptase (TERT) rs2736098 polymorphism was related to the incidence of lung cancer.MethodsWe systematically searched the following three electronic databases: PubMed, Embase, and China National Knowledge Infrastructure (CNKI), for relevant articles. Statistical analysis was performed using the odds ratio (OR) and the corresponding 95% confidence interval (CI).ResultsSeven articles involving 3836 healthy controls and 3637 patients were included in this meta-analysis. TERT rs2736098 polymorphism was significantly related to lung cancer incidence (AA vs. GG: OR=1.83, 95% CI=1.58–2.12; AG vs. GG: OR=1.21, 95% CI=1.10–1.34; Dominant model: OR=1.33, 95% CI=1.22–1.46; Recessive model: OR=1.66, 95% CI=1.44–1.90). Moreover, this polymorphism was found to be correlated with the susceptibility to lung cancer when studies were stratified based on the sample size and the Hardy–Weinberg equilibrium.ConclusionThe present findings indicate that the TERT rs2736098 polymorphism may be a risk factor for the development of lung cancer.

Association between TERT gene polymorphisms and acute myeloid leukemia susceptibility in a Chinese population: a case\u2013control study

BackgroundThe aim of this study was to investigate the association between telomerase reverse transcriptase (TERT) gene polymorphisms and acute myeloid leukemia (AML) susceptibility in a Chinese Han population.MethodsA total of 102 AML patients and 108 healthy controls were enrolled in this case–control study. TERT gene rs2853669 and rs2736100 polymorphisms were genotyped via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Chi-square test was applied to compare polymorphism distributions between case and control groups. The strength of the association between TERT gene polymorphisms and AML susceptibility was evaluated utilizing odds ratio (OR) with corresponding 95% confidence interval (CI).ResultsCC genotype and C allele of rs2736100 polymorphism were more frequent in AML patients (P < 0.05), and individuals carrying CC genotype showed higher risk of suffering from AML (OR = 2.632, 95% CI 1.129–6.133). But for rs2853669 polymorphism, no significant differences were detected in either genotype or allele distributions between groups (P > 0.05).ConclusionsThis study suggested a positive association between TERT gene rs2736100 polymorphism and AML susceptibility in Chinese Han population.

The telomerase gene polymorphisms, but not telomere length, increase susceptibility to primary glomerulonephritis/end stage renal diseases in females

BackgroundPrimary glomerulonephritis (GN) is the leading cause of chronic kidney disease (CKD) and frequently progresses into end stage renal diseases (ESRDs). Shorter leukocyte telomere length (LTL) has been implicated in the CKD susceptibility and diminished kidney function, however, it is unclear whether the variants in telomerase genes contribute to risk to GN/CKD/ESRD. Here we address this issue by determining their association with the genetic variants of rs12696304 at the telomerase RNA component (TERC) and rs2736100 at the telomerase reverse transcriptase (TERT) loci.MethodsThe study includes 769 patients (243 primary GN-derived CKD and 526 ESRD cases) and sex-/age-matched healthy controls. Genomic DNA was extracted from peripheral blood of both controls and patients. Genotyping of rs12696304 and rs2736100 variants was carried out using PCR-based assays. Leukocyte telomere length (LTL) was determined using quantitative PCR (qPCR).ResultsA significantly higher frequency of TERC rs12696304 G allele was observed in patients and associated with increased disease risk (C vs G: OR = 1.334, 95% CI 1.112–1.586, P = 0.001; CC + GC vs GG: OR = 1.334, 95% CI 1.122–1.586, P = 0.001). Further analyses showed that such significant differences were only present between female controls and patients (C vs G: OR = 1.483, 95% CI 1.140–1.929, P = 0.003; CC + GC vs CC: OR = 1.692, 95% CI 1.202–2.383, P = 0.003), but not males. There were no differences in rs2736100 variants between controls and patients, but female ESRD patients carried significantly higher C allele frequencies than did female controls (A vs C: OR = 1.306, 95% CI 1.005–1.698, P = 0.046; AA vs CC: OR = 1.781, 95% CI 1.033–3.070, P = 0.037). There was no difference in LTL between controls and patients.ConclusionsOur results reveal that the TERC rs12696304 and TERT rs2736100 polymorphisms, but not LTL per se, contribute to GN/CDK/ESRD risk.

Role of TERT Gene in Relationship between Body Fat Percentage with the Modifiable Risk Factors of Cardiometabolic Disease in Minangkabau Premenopausal

Background: &#x0D; Cardiometabolic disease risk is increasing in the premenopausal phase of women life. This study aims to relationship body fat percentage with the modifiable risk factors of cardiometabolic disease in Minangkabau premenopausal people.&#x0D; Methods: A cross-sectional study was conducted in 111 Minangkabau premenopausal people, aged 40 – 55 years old at Padang City in West Sumatera, Indonesia. Body fat percentage analyzed by Bioelectrical Impedance Analyzer (BIA). Fasting blood glucose and lipid profile was examined from venous blood. Data were analyzed by using a Rank-Spearman correlation test with significant levels p&lt;0.05.&#x0D; Results:Average body fat percentage of subjects 36.23 ± 6.9, fasting blood glucose 101.52 ± 12.3 mg/dL; total cholesterol 193.99±41.5 mg/dL; triglyceride 113.76±37.9 mg/dL mg/dL; LDL-cholesterol 120.59±45.7 mg/dL and HDL-cholesterol 53.52±15.6 mg/dL. Body fat percentage has a significant correlation with triglyceride (r=0.368; p=0.001), and HDL-cholesterol levels (r=-0.307; p=0.006 ) just in subject with polymorphism, but does not have a significant correlation with another biomarker.&#x0D; Conclusion: Body fat percentage correlates with triglyceride and HDL cholesterol in Minangkabau premenopausal women who have polymorphism of TERT Gene.&#x0D; BACKGROUND: Cardiometabolic disease risk is increasing in the premenopausal phase of women life. The telomerase reverse transcriptase (TERT) gene is a gene that plays a role in protecting telomeres from progressive shortening. Telomere shortening is associated with the incidence of cardiometabolic disease.&#x0D; AIM: This study aims to elucidate the relationship body fat percentage with the modifiable risk factors of cardiometabolic disease in Minangkabau premenopausal people.&#x0D; METHODS: A cross-sectional study was conducted in 111 Minangkabau premenopausal people aged 40–55 years old at Padang City in West Sumatera, Indonesia. Body fat percentage analyzed by bioelectrical impedance analyzer. Fasting blood glucose and lipid profile were examined from venous blood. Polymorphism of the TERT rs2736098 gene was analyzed by a polymerase chain reaction. Data were analyzed using Spearman’s rank correlation test with significant levels p &lt; 0.05.&#x0D; RESULTS: Average body fat percentage of subjects was 36.23 ± 6.9, fasting blood glucose was 101.52 ± 12.3 mg/dL; total cholesterol was 193.99 ± 41.5 mg/dL; triglyceride was 113.76 ± 37.9 mg/dL; LDL-cholesterol was 120.59 ± 45.7 mg/dL and HDL-cholesterol was 53.52±15.6 mg/dL. Body fat percentage has a significant correlation with triglyceride (r = 0.368; p = 0.001) and HDL-cholesterol levels (r = −0.307; p = 0.006) just in subject with polymorphism but does not have a significant correlation with another biomarker.&#x0D; CONCLUSION: Body fat percentage correlates with triglyceride and HDL cholesterol in Minangkabau premenopausal women who have polymorphism of TERT gene.

Association between Telomere-Related Polymorphisms and the Risk of IPF and COPD as a Precursor Lesion of Lung Cancer: Findings from the Fukuoka Tobacco-Related Lung Disease (FOLD) Registry.

Lung cancer coexisting with idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD) can lead to poor prognosis. Telomere-related polymorphisms may be implicated in the pathogenesis of these three lung diseases. As to elucidate the mechanism of lung cancer via IPF or COPD may enable early detection and early treatment of the disease, we firstly examined the association between telomere-related polymorphisms and the risk of IPF and COPD in a case-control study. A total of 572 patients with IPF (n = 155) or COPD (n = 417), who were derived from our on-going cohort study, and controls (n = 379), who were derived from our previous case-control study, were included in this study. Telomerase reverse transcriptase (TERT) rs2736100, telomere RNA component (TERC) rs1881984, and oligonucleotide/oligosaccharide-binding fold containing1 (OBFC1) rs11191865 were genotyped with real-time PCR using TaqMan fluorescent probes. Unconditional logistic regression was used to assess the adjusted odds ratios and 95% confidence intervals. TERT rs2736100 was significantly associated with the risk of IPF; increases in the number of this risk allele increased the risk of IPF (Ptrend = 0.008). Similarly, TERT rs2736100 was associated with the risk of COPD. In regard to the combined action of the three loci, increasing numbers of "at-risk" genotypes increased the risk of IPF in a dose-dependent manner (P trend=0.003). TERT rs2736100 was associated with the risks of both IPF and COPD in a Japanese population. A combination of the "at-risk" genotypes might be important to identify the population at risk for IPF more clearly.

Association Between TERT rs2736098 Polymorphisms and Cancer Risk-A Meta-Analysis.

Background: Cancer remains a leading cause of death and constitutes an enormous burden on society worldwide. The association between the human telomerase reverse transcriptase (TERT) gene variant rs2736098 polymorphisms and cancer predisposition remain inconclusive.Objective and methods: Databases including Pubmed and Embase were systematically searched from inception to September 15, 2017 to retrieve studies investigating the association between the TERT variant rs2736098 polymorphisms and cancer risk in accordance with previously determined exclusion and inclusion criteria. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were evaluated using random or fixed effects models.Results: Thirty-one case-control studies from 29 articles with 15,837 cases and 19,263 controls were screened out after a systematic search. Pooled analysis demonstrated that the TERT variant rs2736098 G > A polymorphism was significantly correlated with cancer risk in all populations (A vs. G: OR = 1.134, 95% CI = 1.051–1.224, P = 0.001; AA vs. GG: OR = 1.280, 95% CI = 1.087–1.508, P = 0.003; GA vs. GG: OR = 1.125, 95% CI = 1.020–1.240, P = 0.018; GA/AA vs. GG: OR = 1.159, 95% CI = 1.047–1.283, P = 0.004). In the subgroup analysis based on cancer type, the TERT rs2736098 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.Conclusions: This meta-analysis demonstrated significant correlations between the TERT variant rs2736098 polymorphisms and cancer susceptibility. The A allele in the rs2736098 G > A polymorphism contributes to susceptibility in many types of cancer, especially lung cancer and bladder cancer.

Genetic polymorphisms in the TERT-CLPTM1L region and lung cancer susceptibility in Chinese males.

The objective of the present study was to analyze the relationship between genetic polymorphisms of the rs2736098 locus of the telomerase reverse transcriptase (TERT) gene and the rs401681 locus of the cleft lip and palate transmembrane protein 1 (CLPTM1L) gene and the risk of developing lung cancer in males in Jinzhou. A total of 214 lung cancer patients who were admitted in Jinzhou Medical University were analyzed, and 216 healthy males were selected as controls. Venous blood from all subjects and data on relevant risk factors were collected. DNA was extracted from peripheral blood by the phenol-chloroform method. Real-time fluorescent quantitative PCR (TaqMan real-time PCR) was used for DNA amplification. The genotyping results of the genetic polymorphisms of the TERT rs2736098 and CLPTM1L rs401681 loci were detected. The risk of developing lung cancer in the population with the TERT rs2736098 locus carrying the T allele was 1.614 times that with the TERT rs2736098 locus carrying the C allele after adjustment of the age factor. The risk of developing lung cancer in the population carrying the TT mutant genotype and the CT genotype increased significantly compared with that carrying the CC wild genotype [odds ratio (OR)=1.815, 95% CI=1.132–2.957; OR=2.417, 95% CI=1.158–4.943]. Based on a comparison between the combination of the two mutant genotypes (CT+TT) and the wild homozygous genotype (CC), the mutant genotype increased the risk of developing lung cancer (OR=1.955, 95% CI=1.213–3.157). The risk of developing lung cancer in the population with the CLPTM1L rs401681 locus carrying the T allele was 1.399 times that carrying the C allele (OR=1.343, 95% CI=1.035–1.978). The population with the TERT rs2736098 locus carrying the mutant genotype (CT+TT) was associated with the number of tumors (OR=0.553, 95% CI=0.236–0.928). In conclusion, in males, the TERT rs2736098 and CLPTM1L rs401681 T alleles are the susceptibility factors for developing lung cancer. Individuals, including the smoking population, who carry both the TERT rs2736098 and CLPTM1L rs401681 T alleles are more likely to develop lung cancer.

The TERT rs2736100 polymorphism increases cancer risk: A meta-analysis.

Abnormal telomerase activity is implicated in cancer initiation and development. The rs2736100 T > G polymorphism in the telomerase reverse transcriptase (TERT) gene, which encodes the telomerase catalytic subunit, has been associated with increased cancer risk. We conducted a meta-analysis to more precisely assess this association. After a comprehensive literature search of the PubMed and EMBASE databases up to November 1, 2016, 61 articles with 72 studies comprising 108,248 cases and 161,472 controls were included in our meta-analysis. Studies were conducted on various cancer types. The TERT rs2736100 polymorphism was associated with increased overall cancer risk in five genetic models [homozygous model (GG vs. TT): odds ratio (OR) = 1.39, 95% confidence interval (95% CI) = 1.26-1.54, P < 0.001; heterozygous model (TG vs. TT): OR = 1.16, 95% CI = 1.11-1.23, P < 0.001; dominant model (TG + GG vs. TT): OR = 1.23, 95% CI = 1.15-1.31, P < 0.001; recessive model (GG vs. TG + TT): OR = 1.25, 95% CI = 1.16-1.35, P < 0.001; and allele contrast model (G vs. T): OR = 1.17, 95% CI = 1.12-1.23, P < 0.001]. A stratified analysis based on cancer type associated the polymorphism with elevated risk of thyroid cancer, bladder cancer, lung cancer, glioma, myeloproliferative neoplasms, and acute myeloid leukemia. Our results confirm that the TERT rs2736100 polymorphism confers increased overall cancer risk.

Association Between the Telomerase rs2736098_TT Genotype and a Lower Risk of Chronic Hepatitis B and Cirrhosis in Chinese Males.

Objectives:Chronic hepatitis B (CHB) is caused by infection of hepatitis B virus (HBV) and liver cirrhosis (LC) is its most common complication. The accumulated evidence indicates a genetic context of HBV infection phenotypes. Here we determine a potential association of CHB/LC with the genetic variant of telomerase reverse transcriptase (TERT), a key player in aging including immune-senescence.Methods:The study included 227 Chinese CHB patients and 315 sex/age-matched healthy controls. TERT rs2736098 and rs2736100 genotyping was performed using pre-designed TaqMan SNP genotyping assay kits. Leukocyte telomere length (LTL) was determined using quantitative PCR.Results:The rs2736098_CT/CC genotypes were significantly associated with risk of CHB compared to the TT one (OR 2.265, 95% CI 1.202–4.269, P=0.015). A similar association was also found in CHB patients with cirrhosis (CT/CC vs TT: OR 2.398, 95% CI 1.168–4.922, P=0.02). Further analyses showed that the rs2736098_TT genotype difference occurred between male controls and patients (P=0.008) and male CT/CC-carriers exhibited highly increased risk of CHB compared to male controls (CT+CC vs TT, OR 3.182, 95% CI 1.350–7.500, P=0.01). There was no difference in the rs2736100 variants between controls and CHB patients. LTL was not different between cases and controls.Conclusions:The TERT rs2736098_TT genotype is associated with a lower CHB and LC risk in Chinese males, which may have implications in CHB pathogenesis and prevention.

The TERT promoter mutation incidence is modified by germline TERT rs2736098 and rs2736100 polymorphisms in hepatocellular carcinoma.

Telomerase activation via induction of the catalytic component telomerase reverse transcriptase (TERT) plays essential roles in malignant transformation. TERT promoter-activating mutations were recently identified as a novel mechanism to activate telomerase in hepatocellular carcinoma (HCC) and many other malignancies. In addition, single nucleotide polymorphisms (SNPs) in the TERT rs2736098 and rs2736100 are significantly associated with cancer susceptibility. It is currently unclear whether different germline TERT variants modify TERT promoter mutations. Here we analyzed the TERT promoter status and genotyped the TERT SNPs at rs2736098 and rs2736100 in patients with HCC. Thirty percent of HCCs harbored TERT promoter mutations and there was a significant difference in rs2736098 and rs2736100 genotypes between wt and mutant TERT promoter-bearing HCC tumors (P = 0.007 and 0.018, respectively). For rs2736100, the cancer risk genotype CC was significantly associated with a reduced incidence of TERT promoter mutations compared to AA + AC variants [Odds ratio (OR): 0.181, 95% Confidence interval (CI): 0.0543–0.601, P = 0.004]. The rs2736098_CT genotype was significantly associated with the TERT promoter mutation-positive tumors compared to the TT genotype (OR: 5.391, 95% CI: 1.234–23.553, P = 0.025). These differences in genotype distribution did not differ between patients with a wt TERT promoter and controls. The presence of TERT promoter mutations was not associated with clinico-pathological variables. Taken together, the germline TERT genetic background may significantly affect the onset of TERT promoter mutations in HCCs, which provides a better understanding of HCC-related TERT promoter mutations and telomerase regulation in cancer.

Association of monocyte chemoattractant protein-1 rs1024611 and telomerase rs2736100 polymorphisms with susceptibility to pulmonary tuberculosis in Han Chinese population

Pulmonary tuberculosis (PTB) is caused by Mycobacterium tuberculosis infection and accumulated evidence reveals the genetic context of its infection phenotypes. Monocyte chemoattractant protein-1 (MCP-1) rs1024611 variant is shown to be associated with PTB susceptibility in some studies, but significant disparities exist. In addition, telomerase plays a key role in immunocompetence, and the telomerase reverse transcriptase (TERT) polymorphism is associated with susceptibility to different diseases. We, thus, determined the relationship between MCP-1 rs1024611 and TERT rs2736100 variants and PTB susceptibility by genotyping 183 Han Chinese patients with active PTB and 210 ethnicity/age/sex-matched healthy controls. The rs1024611_GG genotype was found at a higher frequency in controls than in patients with PTB. The GA genotype exhibited significantly reduced risk of PTB (P = 0.03). When GA and AA genotypes were grouped together, the GG variant remained at a significantly higher risk for PTB (P = 0.042). Further analyses revealed that the risk occurred in males, but not females (P = 0.037). There was no difference in TERT rs2736100 genotypes between controls and patients, suggesting the lack of association of this genetic variant with PTB risk. Taken together, Han Chinese male rs1024611_GG-carriers exhibit a significantly higher susceptibility to active PTB.

The association between the TERT rs2736100 AC genotype and reduced risk of upper tract urothelial carcinomas in a Han Chinese population.

Upper tract urothelial carcinomas (UTUCs) are originated from urothelium, and consist of renal pelvic carcinomas (RPCs) and ureter carcinomas (UCs). Most UTUCs have already become invasive when diagnosed and there is thus a need to identify high-risk populations for preventive intervention. Recent evidence has accumulated supporting common single nucleotide polymorphisms (SNPs) to be associated with increased risk of various malignancies. However, little is known about susceptibility loci in relation to UTUC development. We genotyped telomerase reverse transcriptase (TERT) rs2736100 variants, the SNP associated with a risk of multiple-types of cancer, in patients with UTUC (n = 212) and evaluated the relationship between the rs2736100 and UTUC risk by comparing to 289 healthy controls. Neither AA nor CC genotypes differed significantly between cases and controls, while the AC-carriers were associated with a reduced risk of UTUC compared to the homozygous AA (OR = 0.583; 95% CI: 0.388 − 0.875; P = 0.012) or AA + CC genotypes (0.613; 95% CI: 0.428 − 0.879; P = 0.010). Further analyses showed that the AC variant conferred a lower risk for early stage UTUCs or those with a wt TERT promoter. When UTUCs were sub-grouped into UCs and RPCs, the AC genotype still predicts a significantly lower risk for UC (P = 0.045, OR = 0.597, 95% CI: 0.370 − 0.963), while at a border line significance for RPC (P = 0.055, OR = 0.597, 95% CI: 0.324 − 0.976). Collectively, the rs2736100 AC variant predicts a reduced risk to develop UTUC.

Combining Telomerase Reverse Transcriptase Genetic Variant rs2736100 with Epidemiologic Factors in the Prediction of Lung Cancer Susceptibility.

Genetic variants from a considerable number of susceptibility loci have been identified in association with cancer risk, but their interaction with epidemiologic factors in lung cancer remains to be defined. We sought to establish a forecasting model for identifying individuals with high-risk of lung cancer by combing gene single-nucleotide polymorphisms with epidemiologic factors. Genotyping and clinical data from 500 lung cancer cases and 500 controls were used for developing the logistic regression model. We found that lung cancer was associated with telomerase reverse transcriptase (TERT) rs2736100 single-nucleotide polymorphism. The TERT rs2736100 model was still significantly associated with lung cancer risk when combined with environmental and lifestyle factors, including lower education, lower BMI, COPD history, heavy cigarettes smoking, heavy cooking emission, and dietary factors (over-consumption of meat and deficiency in fish/shrimp, vegetables, dairy products, and soybean products). These data suggest that combining TERT SNP and epidemiologic factors may be a useful approach to discriminate high and low-risk individuals for lung cancer.