Telomere shortening occurs early during gastrocarcinogenesis

Mu, Yunchuan; Zhang, Qing; Mei, Linhang; Liu, Xiaosun; Yang, Weili; Yu, Jiren

doi:10.1007/s12032-011-9866-3

Cited by 23 publications

(13 citation statements)

References 21 publications

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“…These data are in contrast to the general model of the role played by telomeres in tumor development, i.e. telomere shortening as an early event in carcinogenesis (34,37). However, our results are consistent with several previous studies in which longer telomeres have been associated with absence of metastases in OSCC (35), a low grade in intracranial tumors (38), higher overall survival in lung cancer patients (36), and a lower risk of death in patients with prostate tumors (39).…”

Section: Discussioncontrasting

confidence: 92%

The role of TERT-CLPTM1L SNPs, hTERT expression and telomere length in the pathogenesis of oral squamous cell carcinoma

et al. 2016

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The aim of this study was to assess TERT-CLPTM1L single-nucleotide polymorphisms (SNPs) (rs402710 C/T in the CLPTM1L gene; rs2736100 A/C and rs2736098 G/A in the TERT gene) as risk factors for development of oral squamous cell carcinoma (OSCC), and to investigate the relationship between the analyzed polymorphisms, relative telomere length (RTL), telomerase expression and clinicopathologic characteristics of OSCC in a Serbian population. Paraffin-embedded tumor samples and buccal swabs from cancer-free controls were genotyped using PCR-RFLP, while tumor RTL values and telomerase expression were estimated by real-time PCR and immunohistochemistry, respectively. CLPTM1L rs402710 and TERT rs2736100 polymorphisms were associated with a significantly increased risk of OSCC, and TERT rs2736098 with a significantly decreased risk. No significant association was found between TERT-CLPTM1L polymorphisms, tumor RTL values, telomerase expression, and clinicopathologic features, although a trend towards longer telomeres was evident in telomerase-positive samples and less advanced tumors. Kaplan-Meier survival analysis showed that patients with longer telomeres in their tumors had significantly better overall survival than patients with shorter telomeres. Our research seems to provide strong evidence for an association between CLPTM1L rs402710C/T and TERT rs2736100A/C SNPs and the risk of OSSC, and suggests that higher tumor RTL values and positive hTERT expression may be applicable as early prognostic markers. (J Oral Sci 58, [449][450][451][452][453][454][455][456][457][458] 2016)

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Section: Discussioncontrasting

confidence: 92%

The role of TERT-CLPTM1L SNPs, hTERT expression and telomere length in the pathogenesis of oral squamous cell carcinoma

et al. 2016

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“…In some types of cancers, such as gastric and bladder cancer, shorter RTL in leukocytes was a risk factor of tumorigenesis, [12,13,21] while it was opposite in lung and colorectal cancer. [17,18] …”

Section: Discussionmentioning

confidence: 99%

Association of telomere length in peripheral leukocytes with chronic hepatitis B and hepatocellular carcinoma

Cai

et al. 2016

Medicine

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Background & Objectives:Telomere plays a critical role in the maintenance of genomic stability in eukaryotic chromosomes. More and more findings have shown that alteration in telomere length may involve in normal somatic cells and some diseases, however, whether the telomere length is associated with the development and/or progression of hepatic diseases remains poorly understood.Methods:A case–control study was employed to illustrate the correlation of relative telomere length (RTL) with chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC). In this study, 152 patients with HCC, 212 patients with CHB, and 184 healthy controls were recruited. Genomic deoxyribonucleic acid (DNA) was extracted from the peripheral blood leukocytes, and fluorescence quantitative polymerase chain reaction (FQ-PCR) was used to detect telomere repeated numbers and 36B4 copy numbers. The RTL was calculated by telomere repeat copy number to single-copy gene number ratio in each sample compared with a reference DNA sample.Results:We found that the RTL in HCC group was the longest, followed by CHB group, and healthy control group was the shortest, showing significant statistical differences. When participants were categorized into longer and shorter group according to medium value in healthy controls, individuals who had longer RTL had a significant increased risk of CHB (odds ratio [OR]: 1.83, 95% confidence interval [CI]: 1.22–2.73) when the healthy control was used as the reference groups; furthermore, longer RTL also showed higher incidence of HCC (OR: 3.22, 95% CI: 2.01–5.17; OR: 1.58, 95% CI:1.03–2.41) when healthy control and CHB were used as the reference groups, respectively. When participants were categorized further into 4 groups according to quartile values of RTL in healthy controls, it showed that the longest RTL was also associated with an increased risk of CHB (OR: 2.09, 95% CI: 1.17–3.74) and HCC (OR: 4.31, 95% CI: 2.18–8.52; OR: 2.86, 95% CI: 1.53–5.34) when control and control/CHB group were used as the reference groups, respectively.Conclusion:Our results suggest that the alteration of telomere length in peripheral leukocytes might be involved in the hepatitis B virus infection and HCC events, and RTL might be a potential useful predictor of CHB and HCC.

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“…In gastric cancer not characterized by its DNA MMR status, increasing chromosomal instability, inactivation of p53 tumor suppression, and increasing tumor telomere shortening has been reported [106]. Another evaluation of gastric tumors reported that telomere length was shortest in early stage cancers and then lengthened with increasing stage [107]. In addition, telomere length was increased in the antral mucosa of patients successfully treated for H. pylori infection [108].…”

Section: The Gi Tract Cancers Telomeres and Telomere Maintenance Mementioning

confidence: 99%

Telomeres and telomere dynamics: relevance to cancers of the GI tract

Basu¹,

Skinner²,

Litzelman³

et al. 2013

Expert Review of Gastroenterology & Hepatology

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Summary Aberrations in telomere length and telomere maintenance contribute to cancer development. In this article, we review basic principles of telomere length in normal and tumor tissue and the presence of the two main telomere maintenance pathways as they pertain to GI tract cancer. Peripheral blood telomeres are shorter in patients with many types of GI tract cancers. Telomere length in tumor DNA also appears to shorten early in cancer development. Tumor telomere shortening is often accompanied by telomerase activation to protect genetically damaged DNA from normal cell senescence or apoptosis, allowing immortalized but damaged DNA to persist. Alternative lengthening of telomeres (ALT) is another mechanism used by cancer to maintain telomere length in cancer cells. Telomerase and ALT activators and inhibitors may become important chemopreventive or chemotherapeutic agents as our understanding of telomere biology, specific telomere related phenotypes, and its relationship to carcinogenesis increases.

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Telomere shortening occurs early during gastrocarcinogenesis

Cited by 23 publications

References 21 publications

The role of TERT-CLPTM1L SNPs, hTERT expression and telomere length in the pathogenesis of oral squamous cell carcinoma

The role of TERT-CLPTM1L SNPs, hTERT expression and telomere length in the pathogenesis of oral squamous cell carcinoma

Association of telomere length in peripheral leukocytes with chronic hepatitis B and hepatocellular carcinoma

Telomeres and telomere dynamics: relevance to cancers of the GI tract

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