Tumor Biology

, Volume 36, Issue 11, pp 8703–8713 | Cite as

The relationship between telomere length and clinicopathologic characteristics in colorectal cancers among Tunisian patients

  • Raja Mzahma
  • Maher Kharrat
  • Fadhel Fetiriche
  • Bouasker
  • Mounir Ben Moussa
  • Zoubeir Ben Safta
  • Chadli Dziri
  • AbdelJelil Zaouche
  • Habiba Chaabouni-Bouhamed
Research Article
  • 143 Downloads

Abstract

Alterations in telomere dynamics have emerged as having a causative role in carcinogenesis. Both the telomere attrition contribute to tumor initiation via increasing chromosomal instability and that the telomere elongation induces cell immortalization and leads to tumor progression. The objectives of this study are to investigate the dynamics of telomere length in colorectal cancer (CRC) and the clinicopathological parameters implicated. We measured the relative telomere length (RTL) in cancerous tissues and in corresponding peripheral blood leukocytes (PBL) using quantitative PCR (Q-PCR) from 94 patients with CRC. Telomere length correlated significantly in cancer tissues and corresponding PBL (r = 0.705). Overall, cancer tissue had shorter telomeres than PBL (p = 0.033). In both cancer tissue and PBL, the RTL was significantly correlated with age groups (p = 0.008 and p = 0.012, respectively). The RTL in cancer tissue was significantly longer in rectal tumors (p = 0.04) and in the late stage of tumors (p = 0.01). In PBL, the RTL was significantly correlated with the macroscopic aspect of tumors (p = 0.02). In addition, the telomere-length ratio of cancer to corresponding PBL increased significantly with late-stage groups. Shortening of the telomere was detected in 44.7 %, elongation in 36.2 %, and telomeres were unchanged in 19.1 % of 94 tumors. Telomere shortening occurred more frequently in the early stage of tumors (p = 0.01). This study suggests that the telomere length in PBL is affected by the macroscopic aspect of tumors and that telomere length in cancer tissues is a marker for progression of CRC and depends on tumor-origin site.

Keywords

Telomere length Colorectal cancer Clinicopathologic characteristics 

Notes

Acknowledgements

We thank Dr. Neila Attia Romdhane for her help in the statistics part and Dr. Kawthar Ellouz for her english editing.

References

  1. 1.
    Ju Z, Rudolph KL. Telomeres and telomerase in cancer stem cells. Eur J Cancer. 2006;42:1197–203.CrossRefPubMedGoogle Scholar
  2. 2.
    Lin KW. Telomeres, telomerase, and tumorigenesis a review. Medscape Gen Med. 2004;6(3).Google Scholar
  3. 3.
    Artandi SE, DePinho RA. Telomeres and telomerase in cancer. Carcinogenesis. 2010;31(1):9–18.CrossRefPubMedGoogle Scholar
  4. 4.
    Dhaene K, Marck EV, Parwaresch R. Telomeres, telomerase and cancer: an up-date. Virchows Arch. 2000;437:1–16.CrossRefPubMedGoogle Scholar
  5. 5.
    Gilley D, Herbert BS, Huda N, Tanaka H, Reed T. Factors impacting human telomere homeostasis and age-related disease. Mech Ageing Dev. 2008;129:27–34.CrossRefPubMedGoogle Scholar
  6. 6.
    Londono-Vallejo JA. Telomere instability and cancer. Biogeosciences. 2008;90:73–82.Google Scholar
  7. 7.
    De Cian A, Lacroix L, Douarre C, Temime-Smaali N, Trentesaux C, Riou JF, et al. Targeting telomeres and telomerase. Biogeosciences. 2008;90:131–55.Google Scholar
  8. 8.
    Bollmann FM, Targeting ALT. The role of alternative lengthening of telomeres in pathogenesis and prevention of cancer. Cancer Treat Rev. 2007;33:704–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Desmaze C, Soria JC, Freulet-Marriere MA, Mathieu N, Sabatier L. Telomere-driven genomic instability in cancer cells. Cancer Lett. 2003;194:173–82.CrossRefPubMedGoogle Scholar
  10. 10.
    Raynaud CM, Sabatier L, Philipot O, Olaussen KA, Soria JC. Telomere length, telomeric proteins and genomic instability during the multistep carcinogenic process. Crit Rev Oncol Hemat. 2008;66:99–117.CrossRefGoogle Scholar
  11. 11.
    Baird DM. Mechanisms of telomeric instability. Cytogenet Genome Res. 2008;122:308–14.CrossRefPubMedGoogle Scholar
  12. 12.
    Yakoob J, Guo-Ling HU, Xue-Gong F, Zheng Z. Telomere, telomerase and digestive cancer. World J Gastroenterol. 1999;5(4):334–7.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Greenberg RA. Telomeres crisis and cancer. Curr Mol Med. 2005;5:213–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Shay JW. Determining if telomeres matter in colon cancer initiation or progression. J Natl Cancer Inst. 2013.Google Scholar
  15. 15.
    Svenson U, Roos G. Telomere length as a biological marker in malignancy. Biochim Biophys Acta. 2009;317:1792–4.Google Scholar
  16. 16.
    Frías C, Morán A, de Juan C, Ortega P, Fernández-Marcelo T, Sánchez-Pernaute A, et al. Telomere function in colorectal cancer. World J Gastrointest Oncol. 2009;1(1):3–11.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Gertler R, Rosenberg R, Stricker D, Friederichs J, Hoos A, Werner M, et al. Telomere length and human telomerase reverse transcriptase expression as markers for progression and prognosis of colorectal carcinoma. J Clin Oncol. 2004;22:1807–14.CrossRefPubMedGoogle Scholar
  18. 18.
    Hahn WC. Role of telomeres and telomerase in the pathogenesis of human cancer. J Clin Oncol. 2003;21:2034–43.CrossRefPubMedGoogle Scholar
  19. 19.
    Masutomi K, Hahn WC. Telomerase and tumorigenesis. Cancer Lett. 2003;194:163–72.CrossRefPubMedGoogle Scholar
  20. 20.
    Hackett JA, Greider CW. Balancing instability: dual roles for telomerase and telomere dysfunction in tumorigenesis. Oncogene. 2002;21:619–26.CrossRefPubMedGoogle Scholar
  21. 21.
    Cosme-Blanco W, Chang S. Dual roles of telomere dysfunction in initiation and suppression of tumorigenesis. Exp Cell Res. 2008;314:1973–9.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Rampazzo E, Bertorelle R, Serra L, Terrin L, Candiotto C, Pucciarelli S, et al. Relationship between telomere shortening, genetic instability, and site of tumor origin in colorectal cancers. British J Cancer. 2010;102:1300–5.CrossRefGoogle Scholar
  23. 23.
    Aranda CG, de Juan C, Diaz-Lopez A, Sanchez-Pernaute A, Torres AJ, Diaz-Rubio E, et al. Correlations of telomere length, telomerase activity, and telomeric-repeat binding factor 1 expression in colorectal carcinoma. Cancer. 2006;106:541–51.CrossRefGoogle Scholar
  24. 24.
    Plentz RR, Wiemann SU, Flemming P, Meier PN, Kubicka S, Kreipe H, et al. Telomere shortening of epithelial cells characterises the adenoma-carcinoma transition of human colorectal cancer. Gut. 2003;52:1304–7.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Engelhardt M, Drullinsky P, Guillem J, Moore ASM. Telomerase and telomere length in the development and progression of premalignant lesions to colorectal cancer. Clin Cancer Res. 1997;3:1931–41.PubMedGoogle Scholar
  26. 26.
    Meeker AK, Hicks JL, Iacobuzio-Donahue CA, Montgomery EA, Westra WH, Chan TY, et al. Telomere length abnormalities occur early in the initiation of epithelial carcinogenesis. Clin Cancer Res. 2004;10:3317–26.CrossRefPubMedGoogle Scholar
  27. 27.
    Kim HR, Kim YJ, Kim HJ, Kim SK, Lee JH. Telomere length changes in colorectal cancers and polyps. J Korean Med Sci. 2002;17:360–5.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Takagi S, Kinouchi Y, Hiwatashi N, Chida M, Nagashima F, Takahashi S, et al. Telomere shortening and the clinicopathologic characteristics of human colorectal carcinomas. Cancer. 1999;86:1431–6.CrossRefPubMedGoogle Scholar
  29. 29.
    Cawthon RM. Telomere measurement by quantitative PCR. Nucleic Acids Res. 2002;30:47–52.CrossRefGoogle Scholar
  30. 30.
    Kharrat M, Riahi A, Maazoul F, Mrad R, Chaabouni H. Detection of frequent duplicated CYP21A2 gene carring a Q318X mutation in a general population with quantitative PCR methods. Diagn Mol Pathol. 2011;20(2):123–7.CrossRefPubMedGoogle Scholar
  31. 31.
    Lin KW, Yan J. The telomere length dynamic and methods of its assessment. J Cell Mol Med. 2005;9:977–89.CrossRefPubMedGoogle Scholar
  32. 32.
    Baird DM. New developments in telomere length analysis. Exp Gerontol. 2005;40:363–8.CrossRefPubMedGoogle Scholar
  33. 33.
    Ehrlenbach S, Willeit P, Kiechl S, Willeit J, Reindl M, Schanda K, Kronenberg F, Brandstätter A. Influences on the reduction of relative telomere length over 10 years in the population-based Bruneck Study: introduction of a well-controlled high-throughput assay. Int J Epidemiol. 2009;1–10.Google Scholar
  34. 34.
    Mather KA, Jorm AF, Parslow RA, Christensen H. Is telomere length a biomarker of aging? A review. J Gerontol A Biol Sci Med Sci. 2010.Google Scholar
  35. 35.
    Friedrich U, Griese E, Schwab M, Fritz P, Thon K, Klotz U. Telomere length in different tissues of elderly patients. Mech Ageing Dev. 2000;119:89–99.CrossRefPubMedGoogle Scholar
  36. 36.
    Nakamura K, Furugoria E, Esakib Y, Araib T, Sawabeb M, Okayasu I, et al. Correlation of telomere lengths in normal and cancers tissue in the large bowel. Cancer Lett. 2000;158:179–84.CrossRefPubMedGoogle Scholar
  37. 37.
    Blasco MA. Telomeres and human disease: ageing, cancer and beyond. Nat Rev Genet. 2005;6:611–22.CrossRefPubMedGoogle Scholar
  38. 38.
    Tatsumoto N, Hiyama E, Murakami Y, Imamura Y, Shay JW, Matsuura Y, et al. High telomerase activity is an independent prognostic indicator of poor outcome in colorectal cancer. Clin Cancer Res. 2000;6:2696–701.PubMedGoogle Scholar
  39. 39.
    Biray Avci C. Telomeres and lifestyle choices. Ege University Turkey. Reviews on Selected Topics of Telomere Biology. chapitre 7; p175-193.Google Scholar
  40. 40.
    Kim S, Parks CG, De Roo LA, Chen H, Taylor JA, Cawthon RM, et al. Obesity and weight gain in adulthood and telomere length. Cancer Epidemiol Biomarkers Prev. 2009;18(3):816–20.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Raja Mzahma
    • 1
  • Maher Kharrat
    • 1
  • Fadhel Fetiriche
    • 3
  • Bouasker
    • 4
  • Mounir Ben Moussa
    • 5
  • Zoubeir Ben Safta
    • 3
  • Chadli Dziri
    • 4
  • AbdelJelil Zaouche
    • 5
  • Habiba Chaabouni-Bouhamed
    • 1
    • 2
  1. 1.Human Genetics LaboratoryFaculty of Medicine of TunisTunisTunisia
  2. 2.Human Genetics DepartmentCharles Nicole HospitalTunisTunisia
  3. 3.Department of General Surgery ALa Rabta HospitalTunisTunisia
  4. 4.Department of General Surgery BCharles Nicole HospitalTunisTunisia
  5. 5.Department of General Surgery ACharles Nicole HospitalTunisTunisia

Personalised recommendations