Telomere Length, Cigarette Smoking, and Bladder Cancer Risk in Men and Women

Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 04/2007; 16(4):815-9. DOI: 10.1158/1055-9965.EPI-06-0961
Source: PubMed


Truncated telomeres are among the defining characteristics of most carcinomas. Given the role of telomeres in tumorigenesis, we reasoned that constitutionally short telomeres might be associated with an increased risk of bladder cancer. Using quantitative real-time PCR, we measured relative telomere length in bladder cancer cases and healthy controls and evaluated the association between telomere length, cigarette smoking, and bladder cancer risk in a case-control study nested within the Health Professionals Follow-up Study and a case-control study nested within the Nurses' Health Study. Telomeres were significantly shorter in bladder cancer cases (n = 184) than in controls (n = 192). The mean relative telomere length in cases was 0.23 (SD, 0.16) versus 0.27 (SD, 0.15) in controls (P = 0.001). The adjusted odds ratio for bladder cancer was 1.88 (95% confidence interval, 1.05, 3.36) for individuals in the quartile with the shortest telomeres as compared with individuals in the quartile with the longest telomeres (P(trend) = 0.006). We observed a statistically significant difference in telomere length among men and women (P < 0.001); however, the interaction between gender, telomere length, and bladder cancer risk was not significant. We also observed a significant difference in telomere length across categories of pack-years of smoking (P = 0.01). These findings suggest that truncated telomeres are associated with an increased risk of bladder cancer.

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    • "Several cross-sectional studies demonstrated an inverse relationship between smoking and age-adjusted leukocyte TL (LTL) (Huzen et al., 2014; Weischer et al., 2014; Bendix et al., 2014; Valdes et al., 2005; Morla et al., 2006; McGrath et al., 2007; Song et al., 2010). Moreover, some studies documented a dose–response relationship (Huzen et al., 2014; Valdes et al., 2005; Morla et al., 2006). "
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    ABSTRACT: Leukocyte telomere length (LTL) shortens with age and short LTL has been associated with increased mortality and increased risk for some age-related outcomes. This study aims to analyse the associations of smoking habits with LTL and rate of LTL change per year in older adults. LTL was measured by quantitative PCR at baseline in 3600 older adults, who were enrolled in a population-based cohort study in Germany. For longitudinal analyses, measurements were repeated in blood samples obtained at 8-year follow-up from 1000 participants. Terminal Restriction Fragment analysis was additionally performed in a sub-sample to obtain absolute LTL in base pairs. Multivariate linear regression models were used to estimate associations of smoking habits with baseline LTL and changes in LTL over time. LTL was inversely associated with age (r=-0.090, p<0.0001). Women had longer LTL than men (p<0.0001). Smoking was inversely associated with LTL. On average, current smokers had 73 base pairs (BP) shorter LTL compared to never smokers. Smoking intensity and pack-years of smoking were also inversely associated with LTL, and a positive association was observed with years since smoking cessation. Slower LTL attrition rates were observed in ever smokers over 8years of follow-up. Our cross-sectional analysis supports suggestions that smoking might contribute to shortening of LTL but this relationship could not be shown longitudinally. The overall rather small effect sizes observed for smoking-related variables suggest that LTL reflects smoking-related health hazards only to a very limited extent. Copyright © 2015 Elsevier Inc. All rights reserved.
    Experimental gerontology 08/2015; 70:18-25. DOI:10.1016/j.exger.2015.07.002 · 3.49 Impact Factor
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    • "The S human beta-globin (hbg) gene PCR mix was:iQ SYBR Green Supermix (Bio-Rad) 1x, hbg1 300 nM, hbg2 700 nM, DMSO 1%, DTT 2.5 mM, EDTA 1x. We used the PCR primer sets previously described by McGrath et al. (2007). All samples containing Escherichia coli DNA were heated at 96 C for 10 m and cooled at "
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    ABSTRACT: Several studies have proposed telomere length and telomerase activity as prognostic factors in chronic lymphocytic leukemia (CLL), whereas information addressing the role of telomere-associated genes is limited. We measured relative telomere length (RTL) and TERT expression levels in purified peripheral CD19+ B-cells from seven healthy donors and 77 untreated CLLs in early stage disease (Binet A). Data were correlated with the major biological and cytogenetic markers, global DNA methylation (Alu and LINE-1), and clinical outcome. The expression profiles of telomere-associated genes were also investigated. RTL was decreased in CLLs as compared with controls (P < 0.001); within CLL, a progressive and significant RTL shortening was observed in patients from 13q- through +12, 11q-, and 17p- alterations; short telomeres were significantly associated with unmutated IGHV configuration and global DNA hypomethylation. Decreased RTL was associated with a shorter time to first treatment. A significant upregulation of POT1, TRF1, RAP1, MRE11A, RAD50, and RPA1 transcript levels was observed in CLLs compared with controls. Our study suggests that impairment of telomere/telomerase system represents an early event in CLL pathogenesis. Moreover, the correlation between telomere shortening and global DNA hypomethylation supports the involvement of DNA hypomethylation to increase chromosome instability. © 2014 Wiley Periodicals, Inc.
    Genes Chromosomes and Cancer 07/2014; 53(7). DOI:10.1002/gcc.22171 · 4.04 Impact Factor
    • "TL was found to be higher in aneuploid than diploid tumors, but the authors also recognized the presence of some bias in their study, such as the lack of assessment of T1G3 tumors. In 2007, McGrath et al. demonstrated a significant difference in relative TL between men and women; women had greater relative TL than men.[23] At birth, this difference was undetectable, but it manifested in adulthood,[24] probably as a result of exposure to oxidative stress as well as cigarette smoking.[25] "
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    ABSTRACT: Introduction: Shortening of telomere is associated with cellular senescence and cancer. This study aims to investigate the relationship between tumor grade and recurrence in relation to telomere length (TL), telomerase activity (TA) and telomere-binding proteins expression (TBPs) in patients with non-muscle invasive bladder cancer (NMIBC). Materials and Methods: Tumor/healthy tissues were collected from 58 patients (35 with and 23 without NMIBC). Cystoscopy was performed at 3, 6 and 12 months to determine recurrence. Tumor grades and recurrence were correlated with TL, TA and TBPs using the Kruskal–Wallis non-parametric test. Results were considered significant at P < 0.05. Results: Histological evaluation indicated 15 patients (42.9%) with high-grade (HG) and 20 patients (57.1%) with low-grade (LG) NMIBC. TL, TA and TBPs were found to be significantly different in tumors as compared with controls. A significant (P < 0.05) difference in the expression of TBPs was observed in the disease-free mucosa of cancer patients as compared with HG and LG tumors. In the follow-up, a total of 11 tumor recurrences were observed; among these eight recurrences were observed in patients with HG tumors and three in patients with LG tumors. TL, Human telomerase reverse transcriptase (hTERT) (that represents TA) and poly (ADP-ribose) polymerase 1 (PARP-1) in tumor samples and telomeric repeat binding factors TRF1, TRF2 and tankyrase (TANK) in normal mucosa obtained from the tumor group were respectively found to exhibit a positive and negative association with the risk of recurrence. Conclusions: Our study demonstrates that TL, TA and TBPs are altered in tumors and non-cancerous mucosa in patients with papillary urothelial NMIBC. Further studies are warranted to identify their suitability as a potential biomarker.
    Indian Journal of Urology 07/2014; 30(3):245-51. DOI:10.4103/0970-1591.134241
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