Lymphocyte telomere dynamics and telomerase activity in inflammatory bowel disease: effect of drugs and smoking

Getliffe, Katherine M.; Dulaimi, David Al; Martin‐Ruiz, Carmen; Holder, Roger; Zglinicki, Thomas von; Morris, Alan; Nwokolo, Chuka U.

doi:10.1111/j.1365-2036.2005.02311.x

Cited by 21 publications

(13 citation statements)

References 59 publications

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“…The indication of an association between tobacco smoke exposure and TA provided by this work is in agreement with the results of a previous investigation, in which a smoke‐related increase of TA was observed in normal bronchial epithelium of smokers [Yim et al, ]. However, no smoke‐related differences in TA had been reported in previous studies in PBMCs from healthy individuals [Getliffe et al, ; Narducci et al, ; Jeon et al, ; Rentoukas et al, ]: this discrepancy may depend on the different study design, given that none of the cited studies, involving mixed study populations, was specifically designed to evaluate the relationship between smoking habits and TA, while the twin study design applied in the present work allowed a rigorous assessment of the influence of the study variable under identical genetic background.…”

Section: Discussionsupporting

confidence: 92%

Telomerase activity, telomere length and hTERT DNA methylation in peripheral blood mononuclear cells from monozygotic twins with discordant smoking habits

Marcon

Siniscalchi

Andreoli

et al. 2017

Environ and Mol Mutagen

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Increased telomerase expression has been implicated in the pathogenesis of lung cancer and, since the primary cause of lung cancer is smoking, an association between telomerase reactivation and tobacco smoke has been proposed. In this work an investigation has been performed to assess the relationship between tobacco smoke exposure and telomerase activity (TA) in peripheral blood mononuclear cells of healthy smokers. The methylation status of the catalytic subunit of telomerase hTERT was concurrently investigated to assess the possible association between epigenetic modifications of hTERT and TA. Besides, the association between smoke and telomere length (TL) has been evaluated. Healthy monozygotic twins with discordant smoking habits were selected as study population to minimize inter-individual differences because of demographic characteristics and genetic heterogeneity. Statistically significant higher values of TA and TL were observed in smokers compared to nonsmoker co-twins. The multivariate analysis of data showed, besides smoking habits (P = 0.02), an influence of gender (P = 0.006) and BMI (P = 0.001) on TA and a borderline effect of gender (P = 0.05) on TL. DNA methylation analysis, focused on 100 CpG sites mapping in hTERT, highlighted nine CpG sites differentially methylated in smokers. When co-twins were contrasted, selecting as variables the intra-twin difference in TA and hTERT DNA methylation, a statistically significant inverse correlation (P = 0.003) was observed between TA and DNA methylation at the cg05521538 site. In conclusion, these results indicate an association of tobacco smoke with TA and TL and suggest a possible association between smoke-induced epigenetic effects and TA in healthy smokers. Environ. Mol. Mutagen. 58:551-559, 2017. © 2017 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 92%

Telomerase activity, telomere length and hTERT DNA methylation in peripheral blood mononuclear cells from monozygotic twins with discordant smoking habits

Marcon

Siniscalchi

Andreoli

et al. 2017

Environ and Mol Mutagen

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“…This result indicates a partial contribution of age at blood donation to telomere length, consistent with previous observations (46,47). Valdes et al reported a significant reverse dose-dependent relationship of telomere length with smoking pack-years among 1,122 White women ages 18 to 76 years.…”

Section: Discussionsupporting

confidence: 81%

Short Telomere Length and Breast Cancer Risk: A Study in Sister Sets

Shen

Terry²,

Gurvich³

et al. 2007

Cancer Research

138

130

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Telomeres consist of a tandem repeats of the sequence TTAGGG at the ends of chromosomes and play a key role in the maintenance of chromosomal stability. Previous studies indicated that short telomeres are associated with increased risk for human bladder, head and neck, lung, and renal cell cancer. We investigated the association between white blood cell telomere length and breast cancer risk among 268 family sets (287 breast cancer cases and 350 sister controls). Telomere length was assessed by quantitative PCR. The mean telomere length was shorter in cases (mean, 0.70; range, 0.03-1.95) than in unaffected control sisters (mean, 0.74; range, 0.03-2.29), but no significant difference was observed (P = 0.11). When subjects were categorized according to the median telomere length in controls (0.70), affected sisters had shorter telomeres compared with unaffected sisters after adjusting for age at blood donation and smoking status [odds ratio (OR), 1.3; 95% confidence interval (95% CI), 0.9-1.8], but the association was not statistically significant. The association by quartile of telomere length (Q4 shortest versus Q1 longest) also supported an increase in risk from shorter telomere length, although the association was not statistically significant (OR, 1.6; 95% CI, 0.9-2.7). This association was more pronounced among premenopausal women (OR, 2.1; 95% CI, 0.8-5.5) than postmenopausal women (OR, 1.3; 95% CI, 0.5-3.6 for Q4 versus Q1). If these associations are replicated in larger studies, they provide modest epidemiologic evidence that shortened telomere length may be associated with breast cancer risk. [Cancer Res 2007;67(11):5538-44]

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“…Smoking status, diet, socioeconomic status, stress level, and lifestyle might influence telomere dynamics. 62,98–100 The sex hormones directly increase TERT transcription and telomerase activity in human cells. 24,101 Natural and synthetic androgens can restore telomerase activity to normal levels in cells in patients with TERT and TERC mutations 24 ; this probably explains the benefit of these agents in syndromes involving hematopoietic failure.…”

Section: Modulation Of Telomerase Activitymentioning

confidence: 99%