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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2016, Vol. 10 Issue (2) : 191-203    https://doi.org/10.1007/s11684-016-0450-2
RESEARCH ARTICLE
Association between telomere length and survival in cancer patients: a meta-analysis and review of literature
Xinsen Xu,Kai Qu,Qing Pang,Zhixin Wang,Yanyan Zhou,Chang Liu()
Department of Hepatobiliary Surgery, the First Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an 710061, China
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Abstract

The relationship between telomere length and cancer survival has been widely studied. To gain a deeper insight, we reviewed the published studies. A total of 29 studies evaluated telomere length in the peripheral blood; 22 studies evaluated telomere length in the tumor tissue. First, in the peripheral blood studies, for solid tumor patients with shortened telomere length, the combined hazard ratios (HRs) for mortality and tumor progression were 1.21 (95%CI, 1.10–1.32) and 1.71 (95%CI, 1.37–2.13), respectively. Meanwhile, in hematology malignancy, the combined HRs for mortality and tumor progression were 2.83 (95%CI, 2.14–3.74) and 2.65 (95%CI, 2.18–3.22), respectively. Second, in the studies that use tumor tissue, for patients with shortened telomeres, the combined HRs for mortality and tumor progression were 1.26 (95%CI, 0.95–1.66) and 1.65 (95%CI, 1.26–2.15), respectively. In the studies that calculate the telomere length ratios of tumor tissue to adjacent normal mucosa, for patients with lower telomere length ratios, the combined HRs were 0.66 (95%CI, 0.53–0.83) and 0.74 (95%CI, 0.41–1.32) for mortality and tumor progression, respectively. In conclusion, shortened telomere in peripheral blood and tumor tissue might indicate poor survival for cancer patients. However, by calculating the telomere length ratios of tumor tissue to adjacent normal mucosa, the lower ratio might indicate better survival.

Keywords telomere      survival      cancer      meta-analysis     
Corresponding Author(s): Chang Liu   
Just Accepted Date: 25 April 2016   Online First Date: 17 May 2016    Issue Date: 27 May 2016
 Cite this article:   
Xinsen Xu,Kai Qu,Qing Pang, et al. Association between telomere length and survival in cancer patients: a meta-analysis and review of literature[J]. Front. Med., 2016, 10(2): 191-203.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-016-0450-2
https://academic.hep.com.cn/fmd/EN/Y2016/V10/I2/191
Fig.1  Flow diagram illustrating the screening and selection process.
Study Country/?region Cancer type Center Study ?type Treatment Age Cohort ?size Events ?No. DNA ?source Measurement ?methods Cutoff Survival ?analysis Score
PB study
Solid Cancer
Qu 2015 [41] China Gastric cancer Two Prospective Surgical resection 58 693 280 PB PCR(T/S) ROC curve Cox 17
Chen 2015 [40] China Glioma Single Prospective Surgical resection 44 301 194 PB PCR(T/S) Median Cox 16
Lin 2015 [39] US Bladder cancer Two Prospective Not specified 65 464 353 PB PCR(T/S) Median Cox 15
Russo 2014 [38] Italy Bladder cancer Single Prospective Not specified 64 463 113 PB PCR(T/S) Median Cox 16
Kotsopoulos 2014 [29] Canada Ovarian cancer Multicenter Prospective Not specified NA 1042 611 PB PCR(T/S) Quartilea Cox 14
Duggan 2014 [30] US Breast cancer Three Prospective Not specified NA 1183 135 PB PCR(T/S) Median Cox 17
Chen 2014 [31] China Colorectal cancer Two Prospective Surgical resection NA 571 150 PB PCR(T/S) ROC curves Cox 16
Weischer 2013 [32] Denmark Multiple cancer Multicenter Prospective Not specified 62 3142 1730 PB PCR(T/S) Quartilea Cox 14
Liu 2012 [33] China Liver cancer Two Prospective Transarterial ?chemoembolization 54 269 155 PB PCR(T/S) Median Cox 17
Shen 2012 [34] US Breast cancer Multicenter Prospective Not specified NA 1026 192 PB PCR(T/S) Median Cox 13
Willeit 2010 [35] Italy Multiple cancer Single Prospective Not specified NA 92 44 PB PCR(T/S) Tertileb Cox 17
Svenson 2009 [36] Sweden Renal cancer Single Prospective Surgical resection 65 105 32 PB PCR(T/S) Quartilec Cox 14
Svenson 2008 [37] Sweden Breast cancer Single Prospective Surgical resection 57 265 23 PB PCR(T/S) Quartilec Cox 16
hematonosis
Lin 2014 [42] UK Leukemia Two Prospective Not specified 65 200 NA PB STELA assay Median Cox 16
Mansouri 2013 [43] Sweden Leukemia Multicenter Prospective Not specified 64 265 NA PB PCR(T/S) ROC curves Cox 14
Rampazzo 2012 [44] Italy Leukemia Two Prospective Not specified 62 173 NA PB PCR(T/S) Median Cox 15
Spanoudakis 2011 [57] Greece Myeloproliferative ?neoplasms Single Prospective Chemotherapy NA 44 NA PB and ?bone ?marrow FISH ROC curves KM 12
Borssen 2011 [58] Sweden Leukemia Single Prospective Not specified 9 169 37 Bone ?marrow PCR(T/S) Mean Cox 13
Sellmann 2011 [45] Germany Leukemia Single Prospective Not specified NA 78 17 PB Flow-FISH ROC curves Cox 15
Rossi 2010 [46] Italy Leukemia Single Prospective Not specified NA 128 NA PB Southern Reported* Cox 14
Rossi 2009 [47] Italy Leukemia Single Prospective Not specified 61 191 20 PB Southern ROC curves Cox 15
Roos 2008 [48] Germany Leukemia Single Prospective Not specified 56 147 NA PB PCR(T/S) Median Cox 13
Ghaffari 2008 [49] Iran Leukemia Single Prospective Not specified 35 40 7 PB Telo assay CART technique KM 11
Ricca 2007 [50] Italy Leukemia Single Prospective Chemotherapy 62 201 NA PB Southern ROC curves KM 14
Avigad 2007 [51] Israel Ewing sarcoma Single Prospective Not specified 14 32 13 PB Telo assay ROC curves Cox 14
Grabowski 2005 [52] Sweden Leukemia Three Prospective Not specified 66 296 NA PB and ?bone ?marrow PCR(T/S) Median KM 11
Rigolin 2004 [53] Italy Myelodysplastic ?syndromes Single Prospective Not specified 72 55 8 PB Flow-FISH Median KM 13
Hultdin 2003 [54] Sweden Leukemia Two Prospective Not specified 65 61 33 PB and ?bone ?marrow Southern Median KM 12
Bechter 1998 [55] Austria Leukemia Single Prospective Chemotherapy 66 58 19 Bone ?marrow Southern Median KM 14
Iwama 1997 [56] Japan Leukemia Single Prospective Chemotherapy 45 44 18 Bone ?marrow Southern Mean−2×SD KM 14
Tissue study
Tumor tissue
Augustine 2015 [67] US Colorectal cancer Single Prospective Chemotherapy 60 75 NA Tumor PCR(T/S) Median Cox 16
Pezzolo 2014 [68] Italy Neuroblastoma Two Prospective None 2 102 26 Tumor FISH ROC curve Cox 12
Jeon 2014 [66] Korean Lung cancer Single Prospective Surgical resection 63 164 58 Tumor PCR(T/S) Quartiled Cox 17
Jebaraj 2013 [59] Germany Lymphoma Single Prospective Not specified 65 67 NA Tumor PCR(T/S) Median KM 13
Lu 2011 [60] Italy Breast cancer Single Prospective Surgical resection 57 348 60 Tumor PCR(T/S) Median Cox 16
Heaphy 2007 [61] US Breast cancer Multicenter Prospective Not specified 59 530 100 Tumor slot blot Twice of normal Cox 15
Ohali 2006 [62] Israel Neuroblastoma Single Prospective Chemotherapy 2 51 NA Tumor Telo assay ROC curves Cox 15
Fordyce 2006 [63] US Breast cancer Two Prospective Surgical resection 53 140 NA Tumor Slot blot ROC curves Cox 15
Aranda 2005 [64] Spain Colorectal cancer Single Prospective Surgical resection 69 91 NA Tumor Telo assay Median KM 14
Patel 2002 [65] India Head and neck ?cancer Single Prospective Not specified 50 110 NA Tumor Southern Median KM 12
T/N ratio
Zhang 2014 [69] China Esophageal cancer Single Prospective Surgical resection 56 70 41 T/N ratio PCR(T/S) 0.8 Cox 17
Lötsch 2013 [78] Austria Glioblastoma Single Prospective Surgical resection 60 100 NA T/N ratio PCR(T/S) 1 Cox 15
Kuhn 2011 [70] US Ovarian cancer Two Prospective Not specified 57 212 NA T/N ratio Flow-FISH 1 Cox 13
Valls 2011 [71] Spain Colorectal cancer Single Prospective Surgical resection NA 125 47 T/N ratio Southern 1 Cox 16
Baydar 2010 [72] Turkey Prostate cancer Single Prospective Surgical resection 62 57 NA T/N ratio Flow-FISH 1 Cox 17
Gertler 2008 [73] Germany Esophagus cancer Single Prospective Surgical resection 62 46 21 T/N ratio Telo assay 1.17 Cox 16
Frias 2008 [74] Spain lung cancer Single Prospective Surgical resection 64 83 NA T/N ratio Telo assay 1 Cox 14
Sainger 2007 [75] India Oral cancer Single Prospective Not specified 45 85 NA T/N ratio Southern Median KM 13
Hsu 2005 [76] Taiwan, ?China Esophagus cancer Single Prospective Surgical resection 60 74 49 T/N ratio Telo assay 0.85 Cox 15
Hsu 2004 [79] Taiwan, ?China Lung cancer Single Prospective Surgical resection 64 79 35 T/N ratio Telo assay 0.75 Cox 15
Gertler 2004 [4] Germany Colorectal cancer Single Prospective Surgical resection 65 57 28 T/N ratio Telo assay 0.9 Cox 16
Tab.1  Characteristics of studies included in the meta-analysis
Stratified study No. of studies No. of patients HR (95%CI) Heterogeneity Meta-regression
I2 P P
Study population 0.245
?General population 2 3234 1.34 (1.16–1.54) 88% 0.003
?Special cancer type 11 6382 1.12 (1.00–1.27) 87% <0.001
Sample size 0.721
?≥1000 4 6393 1.21 (1.08–1.35) 47% 0.125
?<1000 9 3223 1.21 (1.03–1.42) 90% <0.001
Cutoff value 0.968
?Median 6 3706 1.06 (0.91–1.23) 87% <0.001
?Other cutoff 7 5910 1.31 (1.17–1.48) 87% <0.001
Quality 0.246
?≥15 9 4301 1.29 (1.10–1.50) 89% <0.001
?<15 4 5315 1.16 (1.04–1.31) 79% 0.002
Area 0.808
?Asia 4 1834 1.20 (0.99–1.44) 93% <0.001
?America/Europe 9 7782 1.21 (1.09–1.35) 82% <0.001
Age 0.592
?≥60 4 4174 1.33 (1.16–1.52) 84% <0.001
?<60 4 1528 0.92 (0.76–1.13) 92% <0.001
Center 0.957
?Multi-center 8 8390 1.20 (1.09–1.33) 87% <0.001
?Single-center 5 1226 1.23 (0.96–1.57) 89% <0.001
Tab.2  Meta-regression analysis of studies that reported the association of peripheral blood telomere length and overall survival of solid cancer patient
Stratified study No. of studies No. of patients HR (95%CI) Heterogeneity Meta-regression
I2 P P
Sample size 0.368
?≥200 4 962 3.07 (2.18–4.32) 83% <0.001
?<200 8 765 2.40 (1.48–3.89) 70% 0.001
Cutoff value 0.982
?Median 6 817 2.65 (1.77–3.98) 62% 0.021
?Other cutoff 6 910 2.99 (2.04–4.40) 83% <0.001
Quality 0.036
?≥15 2 391 13.2 (6.06–27.99) 0% 0.96
?<15 10 1336 2.32 (1.65–3.02) 64% 0.003
Area 0.988
?Asia 2 84 4.26 (1.65–10.99) 45% 0.17
?Europe/Oceania 10 1643 2.72 (2.03–3.64) 77% <0.001
Age 0.140
?≥60 8 1327 3.27 (2.39–4.48) 71% 0.001
?<60 4 400 1.59 (0.85–2.95) 79% 0.002
Center 0.947
?Multi-center 4 822 2.60 (1.84–3.69) 77% 0.005
?Single-center 8 905 3.27 (2.05–5.22) 76% <0.001
Method 0.021
?PCR 4 877 1.70 (1.20–2.42) 72% 0.014
?Non-PCR 8 850 6.63 (4.20–10.49) 36% 0.14
Tab.3  Meta-regression analysis of studies that reported the association of peripheral blood telomere length and overall survival of hematology malignancy patients
Fig.2  Forest plot of hazard ratios of patient survival in all studies focusing on telomere length in peripheral blood. (A) Overall survival in patients with solid cancer. (B) Progression-free survival in patients with solid cancer. (C) Overall survival in patients with hematology malignancy. (D) Progression-free survival in patients with hematology malignancy. HR>1 implies a survival disadvantage for the group with a short telomere length.
Fig.3  Forest plots of hazard ratios of patient survival in all studies focusing on telomere length in tumor tissue or telomere length ratios of tumor tissue to adjacent normal mucosa. (A) Overall survival of patients with telomere length evaluated in tumor tissue. (B) Progression-free survival of patients with telomere length evaluated in tumor tissue. (C) Overall survival of patients evaluating telomere length ratios of tumor tissue to adjacent normal mucosa. (D) Progression-free survival of patients evaluating telomere length ratios of tumor tissue to adjacent normal mucosa. HR>1 implies a survival disadvantage for the group with a short telomere length.
1 Blackburn EH. Switching and signaling at the telomere. Cell 2001; 106(6): 661–673
https://doi.org/10.1016/S0092-8674(01)00492-5 pmid: 11572773
2 Mathon NF, Lloyd AC. Cell senescence and cancer. Nat Rev Cancer 2001; 1(3): 203–213
https://doi.org/10.1038/35106045 pmid: 11902575
3 Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL, Shay JW. Specific association of human telomerase activity with immortal cells and cancer. Science 1994; 266(5193): 2011–2015
https://doi.org/10.1126/science.7605428 pmid: 7605428
4 Gertler R, Rosenberg R, Stricker D, Friederichs J, Hoos A, Werner M, Ulm K, Holzmann B, Nekarda H, Siewert JR. Telomere length and human telomerase reverse transcriptase expression as markers for progression and prognosis of colorectal carcinoma. J Clin Oncol 2004; 22(10): 1807–1814
https://doi.org/10.1200/JCO.2004.09.160 pmid: 15143073
5 Artandi SE, Chang S, Lee SL, Alson S, Gottlieb GJ, Chin L, DePinho RA. Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice. Nature 2000; 406(6796): 641–645
https://doi.org/10.1038/35020592 pmid: 10949306
6 Rudolph KL, Millard M, Bosenberg MW, DePinho RA. Telomere dysfunction and evolution of intestinal carcinoma in mice and humans. Nat Genet 2001; 28(2): 155–159
https://doi.org/10.1038/88871 pmid: 11381263
7 Ma H, Zhou Z, Wei S, Liu Z, Pooley KA, Dunning AM, Svenson U, Roos G, Hosgood HD 3rd, Shen M, Wei Q. Shortened telomere length is associated with increased risk of cancer: a meta-analysis. PLoS ONE 2011; 6(6): e20466
https://doi.org/10.1371/journal.pone.0020466 pmid: 21695195
8 McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM; the Statistics Subcommittee of the NCI-EORTC Working Group on Cancer Diagnostics. REporting recommendations for tumour MARKer prognostic studies (REMARK). Br J Cancer 2005; 93(4): 387–391
https://doi.org/10.1038/sj.bjc.6602678 pmid: 16106245
9 Hayes DF, Ethier S, Lippman ME. New guidelines for reporting of tumor marker studies in breast cancer research and treatment: REMARK. Breast Cancer Res Treat 2006; 100(2): 237–238
https://doi.org/10.1007/s10549-006-9253-5 pmid: 16773436
10 McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM; Statistics Subcommittee of NCI-EORTC Working Group on Cancer Diagnostics. REporting recommendations for tumor MARKer prognostic studies (REMARK). Breast Cancer Res Treat 2006; 100(2): 229–235
https://doi.org/10.1007/s10549-006-9242-8 pmid: 16932852
11 Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 2007; 8(1): 16
https://doi.org/10.1186/1745-6215-8-16 pmid: 17555582
12 Ohyashiki JH, Ohyashiki K, Fujimura T, Kawakubo K, Shimamoto T, Iwabuchi A, Toyama K. Telomere shortening associated with disease evolution patterns in myelodysplastic syndromes. Cancer Res 1994; 54(13): 3557–3560
pmid: 8012981
13 Donaldson L, Fordyce C, Gilliland F, Smith A, Feddersen R, Joste N, Moyzis R, Griffith J. Association between outcome and telomere DNA content in prostate cancer. J Urol 1999; 162(5): 1788–1792
https://doi.org/10.1016/S0022-5347(05)68239-0 pmid: 10524936
14 Martinez-Delgado B, Gallardo M, Tanic M, Yanowsky K, Inglada-Perez L, Barroso A, Rodriguez-Pinilla M, Cañamero M, Blasco MA, Benitez J. Short telomeres are frequent in hereditary breast tumors and are associated with high tumor grade. Breast Cancer Res Treat 2013; 141(2): 231–242
https://doi.org/10.1007/s10549-013-2696-6 pmid: 24036693
15 Heaphy CM, Yoon GS, Peskoe SB, Joshu CE, Lee TK, Giovannucci E, Mucci LA, Kenfield SA, Stampfer MJ, Hicks JL, De Marzo AM, Platz EA, Meeker AK. Prostate cancer cell telomere length variability and stromal cell telomere length as prognostic markers for metastasis and death. Cancer Discov 2013; 3(10): 1130–1141
https://doi.org/10.1158/2159-8290.CD-13-0135 pmid: 23779129
16 La Torre D, Aguennouz M, Conti A, Giusa M, Raffa G, Abbritti RV, Germano’ A, Angileri FF. Potential clinical role of telomere length in human glioblastoma. Transl Med UniSa 2011; 1: 243–270
pmid: 23905037
17 Damle RN, Batliwalla FM, Ghiotto F, Valetto A, Albesiano E, Sison C, Allen SL, Kolitz J, Vinciguerra VP, Kudalkar P, Wasil T, Rai KR, Ferrarini M, Gregersen PK, Chiorazzi N. Telomere length and telomerase activity delineate distinctive replicative features of the B-CLL subgroups defined by immunoglobulin V gene mutations. Blood 2004; 103(2): 375–382
https://doi.org/10.1182/blood-2003-04-1345 pmid: 14504108
18 Yoon SY, Sung HJ, Park KH, Choi IK, Kim SJ, Oh SC, Seo JH, Choi CW, Kim BS, Shin SW, Kim YH, Kim JS. Telomere length shortening of peripheral blood mononuclear cells in solid-cancer patients undergoing standard-dose chemotherapy might be correlated with good treatment response and neutropenia severity. Acta Haematol 2007; 118(1): 30–37
https://doi.org/10.1159/000101558 pmid: 17429195
19 Kubuki Y, Suzuki M, Sasaki H, Toyama T, Yamashita K, Maeda K, Ido A, Matsuoka H, Okayama A, Nakanishi T, Tsubouchi H. Telomerase activity and telomere length as prognostic factors of adult T-cell leukemia. Leuk Lymphoma 2005; 46(3): 393–399
https://doi.org/10.1080/10428190400018349 pmid: 15621829
20 Sieglová Z, Zilovcová S, Cermák J, Ríhová H, Brezinová D, Dvoráková R, Marková M, Maaloufová J, Sajdová J, Brezinová J, Zemanová Z, Michalová K. Dynamics of telomere erosion and its association with genome instability in myelodysplastic syndromes (MDS) and acute myelogenous leukemia arising from MDS: a marker of disease prognosis? Leuk Res 2004; 28(10): 1013–1021
https://doi.org/10.1016/j.leukres.2003.11.020 pmid: 15289012
21 Wu KD, Orme LM, Shaughnessy J Jr, Jacobson J, Barlogie B, Moore MA. Telomerase and telomere length in multiple myeloma: correlations with disease heterogeneity, cytogenetic status, and overall survival. Blood 2003; 101(12): 4982–4989
https://doi.org/10.1182/blood-2002-11-3451 pmid: 12609839
22 Brümmendorf TH, Holyoake TL, Rufer N, Barnett MJ, Schulzer M, Eaves CJ, Eaves AC, Lansdorp PM. Prognostic implications of differences in telomere length between normal and malignant cells from patients with chronic myeloid leukemia measured by flow cytometry. Blood 2000; 95(6): 1883–1890
pmid: 10706851
23 Oh BK, Kim H, Park YN, Yoo JE, Choi J, Kim KS, Lee JJ, Park C. High telomerase activity and long telomeres in advanced hepatocellular carcinomas with poor prognosis. Lab Invest 2008; 88(2): 144–152
https://doi.org/10.1038/labinvest.3700710 pmid: 18158557
24 Rosenberg R, Gertler R, Stricker D, Lassmann S, Werner M, Nekarda H, Siewert JR. Telomere length and hTERT expression in patients with colorectal carcinoma. Recent Results Cancer Res 2003; 162: 177–181
https://doi.org/10.1007/978-3-642-59349-9_16 pmid: 12790332
25 Hirashima T, Komiya T, Nitta T, Takada Y, Kobayashi M, Masuda N, Matui K, Takada M, Kikui M, Yasumitu T, Ohno A, Nakagawa K, Fukuoka M, Kawase I. Prognostic significance of telomeric repeat length alterations in pathological stage I-IIIA non-small cell lung cancer. Anticancer Res 2000; 20(3B): 2181–2187
pmid: 10928174
26 Yan S, Han B, Wu Y, Zhou D, Zhao Y. Telomerase gene mutation screening and telomere overhang detection in Chinese patients with acute myeloid leukemia. Leuk Lymphoma 2013; 54(7): 1437–1441
https://doi.org/10.3109/10428194.2012.729834 pmid: 23157242
27 Boscolo-Rizzo P, Rampazzo E, Perissinotto E, Piano MA, Giunco S, Baboci L, Spinato G, Spinato R, Tirelli G, Da Mosto MC, Del Mistro A, De Rossi A. Telomere shortening in mucosa surrounding the tumor: biosensor of field cancerization and prognostic marker of mucosal failure in head and neck squamous cell carcinoma. Oral Oncol 2015; 51(5): 500–507
https://doi.org/10.1016/j.oraloncology.2015.02.100 pmid: 25771075
28 Willeit P, Willeit J, Kloss-Brandstätter A, Kronenberg F, Kiechl S. Fifteen-year follow-up of association between telomere length and incident cancer and cancer mortality. JAMA 2011; 306(1): 42–44
https://doi.org/10.1001/jama.2011.901 pmid: 21730239
29 Kotsopoulos J, Prescott J, De Vivo I, Fan I, Mclaughlin J, Rosen B, Risch H, Sun P, Narod SA. Telomere length and mortality following a diagnosis of ovarian cancer. Cancer Epidemiol Biomarkers Prev 2014; 23(11): 2603–2606
https://doi.org/10.1158/1055-9965.EPI-14-0885 pmid: 25159293
30 Duggan C, Risques R, Alfano C, Prunkard D, Imayama I, Holte S, Baumgartner K, Baumgartner R, Bernstein L, Ballard-Barbash R, Rabinovitch P, McTiernan A. Change in peripheral blood leukocyte telomere length and mortality in breast cancer survivors. J Natl Cancer Inst 2014; 106(4): dju035
https://doi.org/10.1093/jnci/dju035 pmid: 24627273
31 Chen Y, Qu F, He X, Bao G, Liu X, Wan S, Xing J. Short leukocyte telomere length predicts poor prognosis and indicates altered immune functions in colorectal cancer patients. Ann Oncol 2014; 25(4): 869–876
https://doi.org/10.1093/annonc/mdu016 pmid: 24608194
32 Weischer M, Nordestgaard BG, Cawthon RM, Freiberg JJ, Tybjærg-Hansen A, Bojesen SE. Short telomere length, cancer survival, and cancer risk in 47102 individuals. J Natl Cancer Inst 2013; 105(7): 459–468
https://doi.org/10.1093/jnci/djt016 pmid: 23468462
33 Liu HQ, An JZ, Liu J, Yang YF, Zhang HX, Zhao BY, Li JB, Yang HS, Chen ZN, Xing JL. Leukocyte telomere length predicts overall survival in hepatocellular carcinoma treated with transarterial chemoembolization. Carcinogenesis 2012; 33(5): 1040–1045
https://doi.org/10.1093/carcin/bgs098 pmid: 22318909
34 Shen J, Gammon MD, Terry MB, Bradshaw PT, Wang Q, Teitelbaum SL, Neugut AI, Santella RM. Genetic polymorphisms in telomere pathway genes, telomere length, and breast cancer survival. Breast Cancer Res Treat 2012; 134(1): 393–400
https://doi.org/10.1007/s10549-012-2058-9 pmid: 22527105
35 Willeit P, Willeit J, Mayr A, Weger S, Oberhollenzer F, Brandstätter A, Kronenberg F, Kiechl S. Telomere length and risk of incident cancer and cancer mortality. JAMA 2010; 304(1): 69–75
https://doi.org/10.1001/jama.2010.897 pmid: 20606151
36 Svenson U, Ljungberg B, Roos G. Telomere length in peripheral blood predicts survival in clear cell renal cell carcinoma. Cancer Res 2009; 69(7): 2896–2901
https://doi.org/10.1158/0008-5472.CAN-08-3513 pmid: 19318563
37 Svenson U, Nordfjäll K, Stegmayr B, Manjer J, Nilsson P, Tavelin B, Henriksson R, Lenner P, Roos G. Breast cancer survival is associated with telomere length in peripheral blood cells. Cancer Res 2008; 68(10): 3618–3623
https://doi.org/10.1158/0008-5472.CAN-07-6497 pmid: 18483243
38 Russo A, Modica F, Guarrera S, Fiorito G, Pardini B, Viberti C, Allione A, Critelli R, Bosio A, Casetta G, Cucchiarale G, Destefanis P, Gontero P, Rolle L, Zitella A, Fontana D, Frea B, Vineis P, Sacerdote C, Matullo G. Shorter leukocyte telomere length is independently associated with poor survival in patients with bladder cancer. Cancer Epidemiol Biomarkers Prev 2014; 23(11): 2439–2446
https://doi.org/10.1158/1055-9965.EPI-14-0228 pmid: 25234236
39 Lin J, Blalock JA, Chen M, Ye Y, Gu J, Cohen L, Cinciripini PM, Wu X. Depressive symptoms and short telomere length are associated with increased mortality in bladder cancer patients. Cancer Epidemiol Biomarkers Prev 2015; 24(2): 336–343
https://doi.org/10.1158/1055-9965.EPI-14-0992 pmid: 25416716
40 Chen Y, Wu Y, Huang X, Qu P, Li G, Jin T, Xing J, He S. Leukocyte telomere length: a novel biomarker to predict the prognosis of glioma patients. J Cancer Res Clin Oncol 2015; 141(10): 1739–1747
https://doi.org/10.1007/s00432-015-1938-x pmid: 25702101
41 Qu F, Li R, He X, Li Q, Xie S, Gong L, Ji G, Lu J, Bao G. Short telomere length in peripheral blood leukocyte predicts poor prognosis and indicates an immunosuppressive phenotype in gastric cancer patients. Mol Oncol 2015; 9(3): 727–739
https://doi.org/10.1016/j.molonc.2014.11.008 pmid: 25515040
42 Lin TT, Norris K, Heppel NH, Pratt G, Allan JM, Allsup DJ, Bailey J, Cawkwell L, Hills R, Grimstead JW, Jones RE, Britt-Compton B, Fegan C, Baird DM, Pepper C. Telomere dysfunction accurately predicts clinical outcome in chronic lymphocytic leukaemia, even in patients with early stage disease. Br J Haematol 2014; 167(2): 214–223
https://doi.org/10.1111/bjh.13023 pmid: 24990087
43 Mansouri L, Grabowski P, Degerman S, Svenson U, Gunnarsson R, Cahill N, Smedby KE, Geisler C, Juliusson G, Roos G, Rosenquist R. Short telomere length is associated with NOTCH1/SF3B1/TP53 aberrations and poor outcome in newly diagnosed chronic lymphocytic leukemia patients. Am J Hematol 2013; 88(8): 647–651
https://doi.org/10.1002/ajh.23466 pmid: 23620080
44 Rampazzo E, Bonaldi L, Trentin L, Visco C, Keppel S, Giunco S, Frezzato F, Facco M, Novella E, Giaretta I, Del Bianco P, Semenzato G, De Rossi A. Telomere length and telomerase levels delineate subgroups of B-cell chronic lymphocytic leukemia with different biological characteristics and clinical outcomes. Haematologica 2012; 97(1): 56–63
https://doi.org/10.3324/haematol.2011.049874 pmid: 21933855
45 Sellmann L, de Beer D, Bartels M, Opalka B, Nückel H, Dührsen U, Dürig J, Seifert M, Siemer D, Küppers R, Baerlocher GM, Röth A. Telomeres and prognosis in patients with chronic lymphocytic leukaemia. Int J Hematol 2011; 93(1): 74–82
https://doi.org/10.1007/s12185-010-0750-2 pmid: 21203871
46 Rossi D, Bodoni CL, Zucchetto A, Rasi S, De Paoli L, Fangazio M, Rossi FM, Ladetto M, Gattei V, Gaidano G. Low CD49d expression and long telomere identify a chronic lymphocytic leukemia subset with highly favourable outcome. Am J Hematol 2010; 85(8): 619–622
https://doi.org/10.1002/ajh.21756 pmid: 20578200
47 Rossi D, Lobetti Bodoni C, Genuardi E, Monitillo L, Drandi D, Cerri M, Deambrogi C, Ricca I, Rocci A, Ferrero S, Bernocco E, Capello D, De Paoli L, Bergui L, Boi M, Omedè P, Massaia M, Tarella C, Passera R, Boccadoro M, Gaidano G, Ladetto M. Telomere length is an independent predictor of survival, treatment requirement and Richter’s syndrome transformation in chronic lymphocytic leukemia. Leukemia 2009; 23(6): 1062–1072
https://doi.org/10.1038/leu.2008.399 pmid: 19340005
48 Roos G, Kröber A, Grabowski P, Kienle D, Bühler A, Döhner H, Rosenquist R, Stilgenbauer S. Short telomeres are associated with genetic complexity, high-risk genomic aberrations, and short survival in chronic lymphocytic leukemia. Blood 2008; 111(4): 2246–2252
https://doi.org/10.1182/blood-2007-05-092759 pmid: 18045969
49 Ghaffari SH, Shayan-Asl N, Jamialahmadi AH, Alimoghaddam K, Ghavamzadeh A. Telomerase activity and telomere length in patients with acute promyelocytic leukemia: indicative of proliferative activity, disease progression, and overall survival. Ann Oncol 2008; 19(11): 1927–1934
https://doi.org/10.1093/annonc/mdn394 pmid: 18567608
50 Ricca I, Rocci A, Drandi D, Francese R, Compagno M, Lobetti Bodoni C, De Marco F, Astolfi M, Monitillo L, Vallet S, Calvi R, Ficara F, Omedè P, Rosato R, Gallamini A, Marinone C, Bergui L, Boccadoro M, Tarella C, Ladetto M. Telomere length identifies two different prognostic subgroups among VH-unmutated B-cell chronic lymphocytic leukemia patients. Leukemia 2007; 21(4): 697–705
pmid: 17301820
51 Avigad S, Naumov I, Ohali A, Jeison M, Berco GH, Mardoukh J, Stark B, Ash S, Cohen IJ, Meller I, Kollender Y, Issakov J, Yaniv I. Short telomeres: a novel potential predictor of relapse in Ewing sarcoma. Clin Cancer Res 2007; 13(19): 5777–5783
https://doi.org/10.1158/1078-0432.CCR-07-0308 pmid: 17908968
52 Grabowski P, Hultdin M, Karlsson K, Tobin G, Aleskog A, Thunberg U, Laurell A, Sundström C, Rosenquist R, Roos G. Telomere length as a prognostic parameter in chronic lymphocytic leukemia with special reference to VH gene mutation status. Blood 2005; 105(12): 4807–4812
https://doi.org/10.1182/blood-2004-11-4394 pmid: 15746080
53 Rigolin GM, Porta MD, Bugli AM, Castagnari B, Mauro E, Bragotti LZ, Ciccone M, Cuneo A, Castoldi G. Flow cytometric detection of accelerated telomere shortening in myelodysplastic syndromes: correlations with aetiological and clinical-biological findings. Eur J Haematol 2004; 73(5): 351–358
https://doi.org/10.1111/j.1600-0609.2004.00305.x pmid: 15458514
54 Hultdin M, Rosenquist R, Thunberg U, Tobin G, Norrback KF, Johnson A, Sundström C, Roos G. Association between telomere length and V(H) gene mutation status in chronic lymphocytic leukaemia: clinical and biological implications. Br J Cancer 2003; 88(4): 593–598
https://doi.org/10.1038/sj.bjc.6600763 pmid: 12592375
55 Bechter OE, Eisterer W, Pall G, Hilbe W, Kühr T, Thaler J. Telomere length and telomerase activity predict survival in patients with B cell chronic lymphocytic leukemia. Cancer Res 1998; 58(21): 4918–4922
pmid: 9810000
56 Iwama H, Ohyashiki K, Ohyashiki JH, Hayashi S, Kawakubo K, Shay JW, Toyama K. The relationship between telomere length and therapy-associated cytogenetic responses in patients with chronic myeloid leukemia. Cancer 1997; 79(8): 1552–1560
https://doi.org/10.1002/(SICI)1097-0142(19970415)79:8<1552::AID-CNCR17>3.0.CO;2-X pmid: 9118038
57 Spanoudakis E, Bazdiara I, Pantelidou D, Kotsianidis I, Papadopoulos V, Margaritis D, Xanthopoulidis G, Moustakidis E, Mantzourani S, Bourikas G, Tsatalas C. Dynamics of telomere’s length and telomerase activity in Philadelphia chromosome negative myeloproliferative neoplasms. Leuk Res 2011; 35(4): 459–464
https://doi.org/10.1016/j.leukres.2010.07.042 pmid: 20828816
58 Borssén M, Cullman I, Norén-Nyström U, Sundström C, Porwit A, Forestier E, Roos G. hTERT promoter methylation and telomere length in childhood acute lymphoblastic leukemia: associations with immunophenotype and cytogenetic subgroup. Exp Hematol 2011; 39(12): 1144–1151
https://doi.org/10.1016/j.exphem.2011.08.014 pmid: 21914494
59 Jebaraj BM, Kienle D, Lechel A, Mertens D, Heuberger M, Ott G, Rosenwald A, Barth TF, Möller P, Zenz T, Döhner H, Stilgenbauer S. Telomere length in mantle cell lymphoma. Blood 2013; 121(7): 1184–1187
https://doi.org/10.1182/blood-2012-08-452649 pmid: 23243283
60 Lu L, Zhang C, Zhu G, Irwin M, Risch H, Menato G, Mitidieri M, Katsaros D, Yu H. Telomerase expression and telomere length in breast cancer and their associations with adjuvant treatment and disease outcome. Breast Cancer Res 2011; 13(3): R56
https://doi.org/10.1186/bcr2893 pmid: 21645396
61 Heaphy CM, Baumgartner KB, Bisoffi M, Baumgartner RN, Griffith JK. Telomere DNA content predicts breast cancer-free survival interval. Clin Cancer Res 2007; 13(23): 7037–7043
https://doi.org/10.1158/1078-0432.CCR-07-0432 pmid: 18056180
62 Ohali A, Avigad S, Ash S, Goshen Y, Luria D, Feinmesser M, Zaizov R, Yaniv I. Telomere length is a prognostic factor in neuroblastoma. Cancer 2006; 107(6): 1391–1399
https://doi.org/10.1002/cncr.22132 pmid: 16917952
63 Fordyce CA, Heaphy CM, Bisoffi M, Wyaco JL, Joste NE, Mangalik A, Baumgartner KB, Baumgartner RN, Hunt WC, Griffith JK. Telomere content correlates with stage and prognosis in breast cancer. Breast Cancer Res Treat 2006; 99(2): 193–202
https://doi.org/10.1007/s10549-006-9204-1 pmid: 16752076
64 Garcia-Aranda C, de Juan C, Diaz-Lopez A, Sanchez-Pernaute A, Torres AJ, Diaz-Rubio E, Balibrea JL, Benito M, Iniesta P. Correlations of telomere length, telomerase activity, and telomeric-repeat binding factor 1 expression in colorectal carcinoma. Cancer 2006; 106(3): 541–551
https://doi.org/10.1002/cncr.21625 pmid: 16388518
65 Patel MM, Parekh LJ, Jha FP, Sainger RN, Patel JB, Patel DD, Shah PM, Patel PS. Clinical usefulness of telomerase activation and telomere length in head and neck cancer. Head Neck 2002; 24(12): 1060–1067
https://doi.org/10.1002/hed.10169 pmid: 12454944
66 Jeon HS, Choi YY, Choi JE, Lee WK, Lee E, Yoo SS, Lee SY, Lee J, Cha SI, Kim CH, Park JY. Telomere length of tumor tissues and survival in patients with early stage non-small cell lung cancer. Mol Carcinog 2014; 53(4): 272–279
https://doi.org/10.1002/mc.21972 pmid: 23065897
67 Augustine TA, Baig M, Sood A, Budagov T, Atzmon G, Mariadason JM, Aparo S, Maitra R, Goel S. Telomere length is a novel predictive biomarker of sensitivity to anti-EGFR therapy in metastatic colorectal cancer. Br J Cancer 2015; 112(2): 313–318
https://doi.org/10.1038/bjc.2014.561 pmid: 25412235
68 Pezzolo A, Pistorio A, Gambini C, Haupt R, Ferraro M, Erminio G, De Bernardi B, Garaventa A, Pistoia V. Intratumoral diversity of telomere length in individual neuroblastoma tumors. Oncotarget 2015; 6(10): 7493–7503
https://doi.org/10.18632/oncotarget.2115 pmid: 25595889
69 Zhang DH, Chen JY, Hong CQ, Yi DQ, Wang F, Cui W. High-risk human papillomavirus infection associated with telomere elongation in patients with esophageal squamous cell carcinoma with poor prognosis. Cancer 2014; 120(17): 2673–2683
https://doi.org/10.1002/cncr.28797 pmid: 24840723
70 Kuhn E, Meeker AK, Visvanathan K, Gross AL, Wang TL, Kurman RJ, Shih IeM. Telomere length in different histologic types of ovarian carcinoma with emphasis on clear cell carcinoma. Mod Pathol 2011; 24(8): 1139–1145
https://doi.org/10.1038/modpathol.2011.67 pmid: 21499239
71 Valls C, Piñol C, Reñé JM, Buenestado J, Viñas J. Telomere length is a prognostic factor for overall survival in colorectal cancer. Colorectal Dis 2011; 13(11): 1265–1272
https://doi.org/10.1111/j.1463-1318.2010.02433.x pmid: 20874798
72 Baydar DE, Ozen H, Geyik PO, Gurel B. Can telomere alterations predict biochemical recurrence in prostate adenocarcinoma? A preliminary study. Pathol Res Pract 2010; 206(10): 700–704
https://doi.org/10.1016/j.prp.2010.05.009 pmid: 20674190
73 Gertler R, Doll D, Maak M, Feith M, Rosenberg R. Telomere length and telomerase subunits as diagnostic and prognostic biomarkers in Barrett carcinoma. Cancer 2008; 112(10): 2173–2180
https://doi.org/10.1002/cncr.23419 pmid: 18348304
74 Frías C, García-Aranda C, De Juan C, Morán A, Ortega P, Gómez A, Hernando F, López-Asenjo JA, Torres AJ, Benito M, Iniesta P. Telomere shortening is associated with poor prognosis and telomerase activity correlates with DNA repair impairment in non-small cell lung cancer. Lung Cancer 2008; 60(3): 416–425
https://doi.org/10.1016/j.lungcan.2007.11.001 pmid: 18077053
75 Sainger RN, Telang SD, Shukla SN, Patel PS. Clinical significance of telomere length and associated proteins in oral cancer. Biomark Insights 2007; 2: 9–19
pmid: 19662189
76 Hsu CP, Lee LW, Shai SE, Chen CY. Clinical significance of telomerase and its associate genes expression in the maintenance of telomere length in squamous cell carcinoma of the esophagus. World J Gastroenterol 2005; 11(44): 6941–6947
https://doi.org/10.3748/wjg.v11.i44.6941 pmid: 16437597
77 Peng SY, Chen WJ, Lai PL, Jeng YM, Sheu JC, Hsu HC. High α-fetoprotein level correlates with high stage, early recurrence and poor prognosis of hepatocellular carcinoma: significance of hepatitis virus infection, age, p53 and beta-catenin mutations. Int J Cancer 2004; 112(1): 44–50
https://doi.org/10.1002/ijc.20279 pmid: 15305374
78 Lötsch D, Ghanim B, Laaber M, Wurm G, Weis S, Lenz S, Webersinke G, Pichler J, Berger W, Spiegl-Kreinecker S. Prognostic significance of telomerase-associated parameters in glioblastoma: effect of patient age. Neuro-oncol 2013; 15(4): 423–432
https://doi.org/10.1093/neuonc/nos329 pmid: 23393205
79 Hsu CP, Miaw J, Shai SE, Chen CY. Correlation between telomerase expression and terminal restriction fragment length ratio in non-small cell lung cancer—an adjusted measurement and its clinical significance. Eur J Cardiothorac Surg 2004; 26(2): 425–431
https://doi.org/10.1016/j.ejcts.2004.04.029 pmid: 15296909
80 Zhang C, Chen X, Li L, Zhou Y, Wang C, Hou S. The association between telomere length and cancer prognosis: evidence from a meta-analysis. PLoS ONE 2015; 10(7): e0133174
https://doi.org/10.1371/journal.pone.0133174 pmid: 26177192
81 Svenson U, Roos G. Telomere length as a biological marker in malignancy. Biochim Biophys Acta 2009; 1792(4): 317–323
https://doi.org/10.1016/j.bbadis.2009.01.017 pmid: 19419696
82 Cawthon RM. Telomere measurement by quantitative PCR. Nucleic Acids Res 2002; 30(10): e47
https://doi.org/10.1093/nar/30.10.e47 pmid: 12000852
83 Baird DM, Rowson J, Wynford-Thomas D, Kipling D. Extensive allelic variation and ultrashort telomeres in senescent human cells. Nat Genet 2003; 33(2): 203–207
https://doi.org/10.1038/ng1084 pmid: 12539050
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