Skip to main content

Advertisement

Log in

Leukocyte telomere length in a population-based case–control study of ovarian cancer: a pilot study

  • Original paper
  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

Objectives

Telomeres are structures at chromosome ends that contribute to maintaining genomic integrity. Telomere shortening with repeated cell divisions may lead to genomic instability and carcinogenesis. Studies suggest that shorter telomeres in constitutional DNA are associated with bladder, breast, lung, and renal cancer. Ovarian cancer tissues also have shortened telomeres and increased telomerase activity, suggesting that telomere abnormalities may be related to ovarian cancer.

Methods

We investigated leukocyte telomere length in 99 women with serous ovarian adenocarcinoma and 100 age-matched cancer-free controls enrolled in a population-based case–control study.

Results

Cases tended to have shorter telomeres than controls (P wilcoxon = 0.002). Compared to subjects with telomere lengths in the longest tertile, those in the middle and shortest tertiles showed respective age-adjusted odds ratios (95% confidence intervals) of 2.69 (1.23–5.88) and 3.39 (1.54–7.46) (P trend = 0.002). Strongest associations were found for subjects with poorly differentiated carcinomas (OR = 4.89, 95% CI 1.93–12.34).

Conclusions

This study shows that short leukocyte telomeres are associated with serous ovarian adenocarcinoma. These findings should be confirmed in large, prospective studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Moon IK, Jarstfer MB (2007) The human telomere and its relationship to human disease, therapy, and tissue engineering. Front Biosci 12:4595–4620

    Article  CAS  PubMed  Google Scholar 

  2. Gilley D, Tanaka H, Herbert BS (2005) Telomere dysfunction in aging and cancer. Int J Biochem Cell Biol 37:1000–1013

    Article  CAS  PubMed  Google Scholar 

  3. Maser RS, DePinho RA (2002) Connecting chromosomes, crisis, and cancer. Science 297:565–569

    Article  CAS  PubMed  Google Scholar 

  4. Stewart SA, Weinberg RA (2006) Telomeres: cancer to human aging. Annu Rev Cell Dev Biol 22:531–557

    Article  CAS  PubMed  Google Scholar 

  5. Plentz RR, Caselitz M, Bleck JS et al (2004) Hepatocellular telomere shortening correlates with chromosomal instability and the development of human hepatoma. Hepatology 40:80–86

    Article  CAS  PubMed  Google Scholar 

  6. Rudolph KL, Millard M, Bosenberg MW, DePinho RA (2001) Telomere dysfunction and evolution of intestinal carcinoma in mice and humans. Nat Genet 28:155–159

    Article  CAS  PubMed  Google Scholar 

  7. Blasco MA, Lee HW, Hande MP et al (1997) Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 91:25–34

    Article  CAS  PubMed  Google Scholar 

  8. Shen J, Terry MB, Gurvich I et al (2007) Short telomere length and breast cancer risk: a study in sister sets. Cancer Res 67:5538–5544

    Article  CAS  PubMed  Google Scholar 

  9. Jang JS, Choi YY, Lee WK et al (2008) Telomere length and the risk of lung cancer. Cancer Sci 99:1385–1389

    Article  CAS  PubMed  Google Scholar 

  10. McGrath M, Wong JYY, Michaud D, Hunter DJ, De Vivo I (2007) Telomere length, cigarette smoking, and bladder cancer risk in men and women. Cancer Epidemiol Biomarkers Prev 16:815–819

    Article  CAS  PubMed  Google Scholar 

  11. Wu X, Amos CI, Zhu Y et al (2003) Telomere dysfunction: a potential cancer predisposition factor. J Natl Cancer Inst 95:1211–1218

    Article  CAS  PubMed  Google Scholar 

  12. Shao L, Wood CG, Zhang D et al (2007) Telomere dysfunction in peripheral lymphocytes as a potential predisposition factor for renal cancer. J Urol 178:1492–1496

    Article  PubMed  Google Scholar 

  13. Joshua AM, Vukovic B, Braudey I et al (2007) Telomere attrition in isolated high-grade prostaticintraepithelial neoplasia and surrounding stroma is predictive of prostate cancer. Neoplasia 9:81–89

    Article  CAS  PubMed  Google Scholar 

  14. Kammori M, Takubob K, Nakamurab K et al (2000) Telomerase activity and telomere length in benign and malignant human thyroid tissues. Cancer Lett 159:175–181

    Article  CAS  PubMed  Google Scholar 

  15. Idei T, Sakamoto H, Yamamoto T (2002) Terminal restriction fragments of telomere are detectable in plasma and their length correlates with clinical status of ovarian cancer patients. J Int Med Res 30:244–250

    CAS  PubMed  Google Scholar 

  16. Counter CM, Hirte HW, Bacchetti S, Harley CB (1994) Telomerase activity in human ovarian carcinoma. Proc Natl Acad Sci USA 91:2900–2904

    Article  CAS  PubMed  Google Scholar 

  17. Wang SJ, Sakamoto T, Yasuda S et al (2002) The relationship between telomere length and telomerase activity in gynecologic cancers. Gynecol Oncol 84:81–84

    Article  CAS  PubMed  Google Scholar 

  18. Murakami J, Nagai N, Ohama K, Tahara H, Ide T (1997) Telomerase activity in ovarian tumors. Cancer 80:1085–1092

    Article  CAS  PubMed  Google Scholar 

  19. García-Closas M, Brinton L, Lissowska J et al (2007) Ovarian cancer risk and common variation in the sex hormone-binding globulin gene: a population-based case–control study. BMC Cancer 7:60

    Article  PubMed  CAS  Google Scholar 

  20. Cawthon RM (2009) Telomere length measurement by a novel monochrome multiplex quantitative PCR method. Nucleic Acids Res 37:e21

    Article  PubMed  CAS  Google Scholar 

  21. Schildkraut JM, Bastos E, Berchuck A (1997) Relationship between lifetime ovulatory cycles and overexpression of mutant p53 in epithelial ovarian cancer. J Natl Cancer Inst 89:932–938

    Article  CAS  PubMed  Google Scholar 

  22. Shih IM, Kurman RJ (2004) Ovarian tumorigenesis. A proposed model based on morphological and molecular genetic analysis. Am J Pathol 164:1511–1518

    CAS  PubMed  Google Scholar 

  23. Kurman RJ, Shih I (2008) Pathogenesis of ovarian cancer: lessons from morphology and molecular biology and their clinical implications. Int J Gynecol Pathol 27:151–160

    PubMed  Google Scholar 

  24. Aviv A, Chen W, Gardner JP et al (2009) Leukocyte telomere dynamics: longitudinal findings among young adults in the Bogalusa Heart Study. Am J Epidemiol 169:323–329

    Article  PubMed  Google Scholar 

  25. Unryn BM, Hao D, Gluck S, Riabowol KT (2006) Acceleration of telomere loss by chemotherapy is greater in older patients with locally advanced head and neck cancer. Clin Cancer Res 12:6345–6350

    Article  CAS  PubMed  Google Scholar 

  26. Fern L, Pallis M, Ian CG et al (2004) Clonal haemopoiesis may occur after conventional chemotherapy and is associated with accelerated telomere shortening and defects in the NQO1 pathway; possible mechanisms leading to an increased risk of t-AML/MDS. Br J Haematol 126:63–71

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We are grateful to Drs. Mark H. Greene and Phuong Mai of the National Cancer Institute for helpful comments. We thank Neonila Szeszenia-Dabrowska from the Nofer Institute of Occupational Medicine, Lodz, Poland and Witold Zatonski from the Sklodowska-Curie Institute of Oncology and Cancer Center, Warsaw, Poland for their contributions to the study design and conduct; Anita Soni (Westat, Rockville, MD) for her work on study management for the Polish ovarian cancer study; Pei Chao (IMS, Silver Spring, MD) for her work on data and sample management; and physicians, nurses, interviewers and study participants for their efforts during field work. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics and the Center for Cancer Research; National Institutes of Health (grant CA82838); and American Cancer Society (Grant RSG-00-061-04-CCE).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sharon A. Savage.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mirabello, L., Garcia-Closas, M., Cawthon, R. et al. Leukocyte telomere length in a population-based case–control study of ovarian cancer: a pilot study. Cancer Causes Control 21, 77–82 (2010). https://doi.org/10.1007/s10552-009-9436-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-009-9436-6

Keywords

Navigation