Table Info

Table 2.

Characteristics of studies included in the systematic review and meta-analysis

Author	Year	Region	Sample type	Telomere measurement metric	Measurement method	Patients (n)	Telomere length		Follow-up (years)	Cut-off value	Outcomes (HR, 95% CI, P-value)
Author	Year	Region	Sample type	Telomere measurement metric	Measurement method	Patients (n)	Short (n)	Long (n)	Follow-up (years)	Cut-off value	Outcomes (HR, 95% CI, P-value)
Duggan et al. [17]	2014	America	Blood plasma	Relative telomere length [telomere-to-single copy gene ratio (T/S ratio)]	qPCR	611	306	305	11.2 years	Median (0.81)	OS: 1.33 (0.90–2.00, P = 0.14)
Duggan et al. [17]	2014	America	Blood plasma		qPCR	611	306	305	11.2 years	Median (0.81)	DSS: 1.33 (0.79–2.27, P = 0.27)
Fordyce et al. [18]	2006	America	Tumor tissue	Telomere DNA content (TC)	Slot blot assay	77	35	25	23 years	Tertiles (short < 101%, long > 123%)	DFS: 4.39 (1.47–13.08, P = 0.008)
Gay-Bellile et al. [19]	2016	Europe	Tumor tissue	Relative telomere length (T/S ratio)	qPCR	55	22	23	17 years	Median (1.03)	OS: 2.9 (1.00–8.47, P = 0.050)
Gay-Bellile et al. [19]	2016	Europe	Tumor tissue	Relative telomere length (T/S ratio)	qPCR	55	22	23	17 years	Median (1.03)	DFS: 3.31 (1.38–7.04, P = 0. 0076)
Heaphy et al. [20]	2007	America	Tumor tissue	TC	Slot blot assay	530	444	86	9.16 years	Threshold (short ≤ 200%, long > 200%)	OS: 2.25 (1.09–4.64, P = 0.029)
Heaphy et al. [20]	2007	America	Tumor tissue	TC	Slot blot assay	530	444	86	9.16 years	Threshold (short ≤ 200%, long > 200%)	DFS: 3.14 (1.27–7.76, P = 0.013)
Lu et al. [21]	2011	Europe	Tumor tissue	Relative telomere length (T/S ratio)	qPCR	348	170	166	9 years	Median	OS: 1.27 (0.76–2.13)
Lu et al. [21]	2011	Europe	Tumor tissue	Relative telomere length (T/S ratio)	qPCR	348	170	166	9 years	Median	DFS: 1.19 (0.76–1.82)
Shen et al. [23]	2012	America	Blood plasma	Relative telomere length (T/S ratio)	qPCR	1,026	510	516	9.4 years	Median (0.73)	OS: 0.91 (0.68–1.20)
Shen et al. [23]	2012	America	Blood plasma	Relative telomere length (T/S ratio)	qPCR	1,026	510	516	9.4 years	Median (0.73)	DSS: 0.99 (0.68–1.45)
Simpson et al. [22]	2015	Europe	Tumor tissue	Telomere length (in kb)	Single telomere length analysis (STELA) assay	120	8	112	4.6 years	Median (2.26 kb)	OS: 21.4 (7.9–57.6, P < 0.0001)
Svenson et al. [24]	2008	Europe	Blood plasma	Relative telomere length (T/S ratio)	qPCR	227	114	113	N/A	Median (0.73)	OS: 0.34 (0.16–0.75, P = 0.007)
Vodenkova et al. [25]	2020	Europe	Blood plasma	Relative telomere length (T/S ratio)	qPCR	151	N/A	N/A	N/A	Median	OS: 1.02 (0.34–3.05, P = 0.97)
Vodenkova et al. [25]	2020	Europe	Blood plasma	Relative telomere length (T/S ratio)	qPCR	151	N/A	N/A	N/A	Median	RFS: 0.72 (0.29–1.77, P = 0.47)

OS: overall survival; DSS: disease-specific survival; DFS: disease-free survival; RFS: recurrence-free survival; qPCR: quantitative polymerase chain reaction; HR: hazard ratio; CI: confidence intervals; N/A: not available

Supplementary materials

The supplementary material for this article is available at: https://www.explorationpub.com/uploads/Article/file/1002289_sup_1.pdf.

Declarations

Author contributions

DMAS and KGP: Conceptualization, Data curation, Writing—original draft, Writing—review & editing. TA, DSH, and SLA: Supervision, Validation. All authors provided feedback and approved the final version of the manuscript.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Ethical approval was not required as this study involved the secondary analysis of published data without direct patient interaction.

Consent to participate

Consent to participate was not required as this study involved the secondary analysis of published data without direct patient interaction.

Consent to publication

Not applicable.

Availability of data and materials

All data generated or analyzed for this study are included in the manuscript and the supplementary files.

Funding

Not applicable.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

References

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71:209–49. [DOI] [PubMed]

Lüönd F, Tiede S, Christofori G. Breast cancer as an example of tumour heterogeneity and tumour cell plasticity during malignant progression. Br J Cancer. 2021;125:164–75. [DOI] [PubMed] [PMC]

Łukasiewicz S, Czeczelewski M, Forma A, Baj J, Sitarz R, Stanisławek A. Breast Cancer-Epidemiology, Risk Factors, Classification, Prognostic Markers, and Current Treatment Strategies-An Updated Review. Cancers (Basel). 2021;13:4287. [DOI] [PubMed] [PMC]

Smolarz B, Nowak AZ, Romanowicz H. Breast Cancer-Epidemiology, Classification, Pathogenesis and Treatment (Review of Literature). Cancers (Basel). 2022;14:2569. [DOI] [PubMed] [PMC]

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:e0133174. [DOI] [PubMed] [PMC]

Srinivas N, Rachakonda S, Kumar R. Telomeres and Telomere Length: A General Overview. Cancers (Basel). 2020;12:558. [DOI] [PubMed] [PMC]

Barnes RP, Fouquerel E, Opresko PL. The impact of oxidative DNA damage and stress on telomere homeostasis. Mech Ageing Dev. 2019;177:37–45. [DOI] [PubMed] [PMC]

Moustakli E, Zikopoulos A, Sakaloglou P, Bouba I, Sofikitis N, Georgiou I. Functional association between telomeres, oxidation and mitochondria. Front Reprod Health. 2023;5:1107215. [DOI] [PubMed] [PMC]

Rossiello F, Jurk D, Passos JF, d’Adda di Fagagna F. Telomere dysfunction in ageing and age-related diseases. Nat Cell Biol. 2022;24:135–47. [DOI] [PubMed] [PMC]

10.

Okamoto K, Seimiya H. Revisiting Telomere Shortening in Cancer. Cells. 2019;8:107. [DOI] [PubMed] [PMC]

11.

Dos Santos GA, Viana NI, Pimenta R, de Camargo JA, Guimaraes VR, Romão P, et al. Upregulation of shelterin and CST genes and longer telomeres are associated with unfavorable prognostic characteristics in prostate cancer. Cancer Genet. 2024;284-285:20–9. [DOI] [PubMed]

12.

Ceja-Rangel HA, Sánchez-Suárez P, Castellanos-Juárez E, Peñaroja-Flores R, Arenas-Aranda DJ, Gariglio P, et al. Shorter telomeres and high telomerase activity correlate with a highly aggressive phenotype in breast cancer cell lines. Tumour Biol. 2016;37:11917–26. [DOI] [PubMed]

13.

Kammori M, Sugishita Y, Okamoto T, Kobayashi M, Yamazaki K, Yamada E, et al. Telomere shortening in breast cancer correlates with the pathological features of tumor progression. Oncol Rep. 2015;34:627–32. [DOI] [PubMed]

14.

Murillo-Ortiz BO, García-Corrales K, Martínez-Garza S, Romero-Vázquez MJ, Agustín-Godínez E, Escareño-Gómez A, et al. Association of hTERT expression, Her2Neu, estrogen receptors, progesterone receptors, with telomere length before and at the end of treatment in breast cancer patients. Front Med (Lausanne). 2024;11:1450147. [DOI] [PubMed] [PMC]

15.

Lin F, Huang J, Zhu W, Jiang T, Guo J, Xia W, et al. Prognostic value and immune landscapes of TERT promoter methylation in triple negative breast cancer. Front Immunol. 2023;14:1218987. [DOI] [PubMed] [PMC]

16.

Yang L, Wang B, Jiao X, Zhou C, Chen S, Gao X, et al. TAZ maintains telomere length in TNBC cells by mediating Rad51C expression. Breast Cancer Res. 2021;23:89. [DOI] [PubMed] [PMC]

17.

Duggan C, Risques R, Alfano C, Prunkard D, Imayama I, Holte S, et al. Change in peripheral blood leukocyte telomere length and mortality in breast cancer survivors. J Natl Cancer Inst. 2014;106:dju035. [DOI] [PubMed] [PMC]

18.

Fordyce CA, Heaphy CM, Bisoffi M, Wyaco JL, Joste NE, Mangalik A, et al. Telomere content correlates with stage and prognosis in breast cancer. Breast Cancer Res Treat. 2006;99:193–202. [DOI] [PubMed]

19.

Gay-Bellile M, Romero P, Cayre A, Véronèse L, Privat M, Singh S, et al. ERCC1 and telomere status in breast tumours treated with neoadjuvant chemotherapy and their association with patient prognosis. J Pathol Clin Res. 2016;2:234–46. [DOI] [PubMed] [PMC]

20.

Heaphy CM, Baumgartner KB, Bisoffi M, Baumgartner RN, Griffith JK. Telomere DNA content predicts breast cancer-free survival interval. Clin Cancer Res. 2007;13:7037–43. [DOI] [PubMed]

21.

Lu L, Zhang C, Zhu G, Irwin M, Risch H, Menato G, et al. Telomerase expression and telomere length in breast cancer and their associations with adjuvant treatment and disease outcome. Breast Cancer Res. 2011;13:R56. [DOI] [PubMed] [PMC]

22.

Simpson K, Jones RE, Grimstead JW, Hills R, Pepper C, Baird DM. Telomere fusion threshold identifies a poor prognostic subset of breast cancer patients. Mol Oncol. 2015;9:1186–93. [DOI] [PubMed] [PMC]

23.

Shen J, Gammon MD, Terry MB, Bradshaw PT, Wang Q, Teitelbaum SL, et al. Genetic polymorphisms in telomere pathway genes, telomere length, and breast cancer survival. Breast Cancer Res Treat. 2012;134:393–400. [DOI] [PubMed] [PMC]

24.

Svenson U, Nordfjäll K, Stegmayr B, Manjer J, Nilsson P, Tavelin B, et al. Breast cancer survival is associated with telomere length in peripheral blood cells. Cancer Res. 2008;68:3618–23. [DOI] [PubMed]

25.

Vodenkova S, Kroupa M, Polivkova Z, Musak L, Ambrus M, Schneiderova M, et al. Chromosomal damage and telomere length in peripheral blood lymphocytes of cancer patients. Oncol Rep. 2020;44:2219–30. [DOI] [PubMed]

26.

Ferrer A, Stephens ZD, Kocher JA. Experimental and Computational Approaches to Measure Telomere Length: Recent Advances and Future Directions. Curr Hematol Malig Rep. 2023;18:284–91. [DOI] [PubMed] [PMC]

27.

Thorvaldsdottir B, Aradottir M, Stefansson OA, Bodvarsdottir SK, Eyfjörd JE. Telomere Length Is Predictive of Breast Cancer Risk in BRCA2 Mutation Carriers. Cancer Epidemiol Biomarkers Prev. 2017;26:1248–54. [DOI] [PubMed]

28.

Page MJ, Moher D, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ. 2021;372:n160. [DOI] [PubMed] [PMC]

29.

Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007;8:16. [DOI] [PubMed] [PMC]

30.

Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25:603–5. [DOI] [PubMed]

31.

Halme ALE, McAlpine K, Martini A. Fixed-effect Versus Random-effects Models for Meta-analyses: Random-effects Models. Eur Urol Focus. 2023;9:693–4. [DOI] [PubMed]

32.

Sterne JA, Egger M, Smith GD. Systematic reviews in health care: Investigating and dealing with publication and other biases in meta-analysis. BMJ. 2001;323:101–5. [DOI] [PubMed] [PMC]

33.

Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34. [DOI] [PubMed] [PMC]

34.

Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101. [PubMed]

35.

Ennour-Idrissi K, Maunsell E, Diorio C. Telomere Length and Breast Cancer Prognosis: A Systematic Review. Cancer Epidemiol Biomarkers Prev. 2017;26:3–10. [DOI] [PubMed]

36.

Benites-Zapata VA, Ulloque-Badaracco JR, Alarcón-Braga EA, Fernández-Alonso AM, López-Baena MT, Pérez-López FR. Telomerase activity and telomere length in women with breast cancer or without malignancy: A systematic review and meta-analysis. Maturitas. 2024;180:107882. [DOI] [PubMed]

37.

Maciejowski J, de Lange T. Telomeres in cancer: tumour suppression and genome instability. Nat Rev Mol Cell Biol. 2017;18:175–86. [DOI] [PubMed] [PMC]

38.

Yang J, Liu M, Hong D, Zeng M, Zhang X. The Paradoxical Role of Cellular Senescence in Cancer. Front Cell Dev Biol. 2021;9:722205. [DOI] [PubMed] [PMC]

39.

Lindrose AR, McLester-Davis LWY, Tristano RI, Kataria L, Gadalla SM, Eisenberg DTA, et al. Method comparison studies of telomere length measurement using qPCR approaches: A critical appraisal of the literature. PLoS One. 2021;16:e0245582. [DOI] [PubMed] [PMC]

40.

Aviv A, Hunt SC, Lin J, Cao X, Kimura M, Blackburn E. Impartial comparative analysis of measurement of leukocyte telomere length/DNA content by Southern blots and qPCR. Nucleic Acids Res. 2011;39:e134. [DOI] [PubMed] [PMC]

41.

Lai TP, Wright WE, Shay JW. Comparison of telomere length measurement methods. Philos Trans R Soc Lond B Biol Sci. 2018;373:20160451. [DOI] [PubMed] [PMC]

42.

Wu X, Tanaka H. Aberrant reduction of telomere repetitive sequences in plasma cell-free DNA for early breast cancer detection. Oncotarget. 2015;6:29795–807. [DOI] [PubMed] [PMC]

43.

Holesova Z, Krasnicanova L, Saade R, Pös O, Budis J, Gazdarica J, et al. Telomere Length Changes in Cancer: Insights on Carcinogenesis and Potential for Non-Invasive Diagnostic Strategies. Genes (Basel). 2023;14:715. [DOI] [PubMed] [PMC]

44.

Looi LM, Cheah PL, Ng MH, Yip CH, Mun KS, Rahman NA. Comparison of telomere length and telomerase activation between breast fibroadenoma and infiltrating ductal carcinoma in Malaysian women. Asian Pac J Cancer Prev. 2010;11:713–6. [PubMed]

45.

Alexeeff SE, Schaefer CA, Kvale MN, Shan J, Blackburn EH, Risch N, et al. Telomere length and socioeconomic status at neighborhood and individual levels among 80,000 adults in the Genetic Epidemiology Research on Adult Health and Aging cohort. Environ Epidemiol. 2019;3:e049. [DOI] [PubMed] [PMC]

46.

Hunt SC, Hansen MEB, Verhulst S, McQuillan MA, Beggs W, Lai TP, et al. Genetics and geography of leukocyte telomere length in sub-Saharan Africans. Hum Mol Genet. 2020;29:3014–20. [DOI]

47.

Wang Z, Zhang Z, Guo Y, Shui H, Liu G, Jin T, et al. Shorter Telomere Length Is Associated with Increased Breast Cancer Risk in a Chinese Han Population: A Case-Control Analysis. J Breast Cancer. 2018;21:391–8. [PubMed] [PMC]

48.

Samavat H, Xun X, Jin A, Wang R, Koh WP, Yuan JM. Association between prediagnostic leukocyte telomere length and breast cancer risk: the Singapore Chinese Health Study. Breast Cancer Res. 2019;21:50. [DOI]

49.

De Vivo I, Prescott J, Wong JYY, Kraft P, Hankinson SE, Hunter DJ. A Prospective Study of Relative Telomere Length and Postmenopausal Breast Cancer Risk. Cancer Epidemiol Biomarkers Prev. 2009;18:1152–6. [DOI]

50.

Karimi Forood AM. Mechanisms of telomere dysfunction in cancer from genomic instability to therapy: A review. Int J Sci Res Arc. 2024;13:806–14. [DOI]