Journal of Breast Cancer

Korean Breast Cancer Society (한국유방암학회)
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Shorter Telomere Length Is Associated with Increased Breast Cancer Risk in a Chinese Han Population: A Case-Control Analysis

  • Wang, Zhaoxia (Oncology Department of Integrative Medicine, Luoyang Central Hospital Affiliated to Zhengzhou University) ;
  • Zhang, Zhenxing (Oncology Department of Integrative Medicine, Luoyang Central Hospital Affiliated to Zhengzhou University) ;
  • Guo, Yanling (Oncology Department of Integrative Medicine, Luoyang Central Hospital Affiliated to Zhengzhou University) ;
  • Shui, Huifeng (Oncology Department of Integrative Medicine, Luoyang Central Hospital Affiliated to Zhengzhou University) ;
  • Liu, Guoqi (Oncology Department of Integrative Medicine, Luoyang Central Hospital Affiliated to Zhengzhou University) ;
  • Jin, Tianbo (Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University) ;
  • Wang, Huijie (Oncology Department of Integrative Medicine, Luoyang Central Hospital Affiliated to Zhengzhou University)
  • Received : 2018.03.27
  • Accepted : 2018.09.03
  • Published : 2018.12.31
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Abstract

Purpose: The aim of this study was to investigate the association of telomere length with breast cancer risk. We simultaneously explored the association between telomerase reverse transcriptase gene polymorphisms and telomere length. Methods: We used real-time quantitative polymerase chain reaction to measure relative telomere length (RTL) in genomic DNA extracted from peripheral blood from 183 breast cancer cases and 191 healthy controls. Genotyping was performed using the Sequenom MassARRAY platform. Results: Our results show that breast cancer patients had significantly shorter RTLs than control subjects (p<0.05). When the RTLs were categorized into tertiles, we found that the lowest RTL was significantly associated with increased breast cancer risk compared with the highest RTL (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.40-3.90; p=0.001). Subgroup analyses indicated that risk of breast cancer was also significantly increased in the lowest RTL compared with the highest RTL in age >40 years (OR, 2.41; 95% CI, 1.31-4.43;p=0.005), body mass index ${\leq}24kg/m^2$ (OR, 2.81; 95% CI, 1.55-5.10; p=0.001), and postmenopausal women (OR, 3.94; 95% CI, 1.63-9.51; p=0.002), respectively. In addition, individuals with the AA genotype of rs2853677 have longer telomeres than those of breast cancer patients with the AG genotype (p=0.011). Conclusion: Our results suggest that shorter RTL was associated with an increased risk of breast cancer. An association was found between the AA genotype of rs2853677 and longer RTLs in the case group. Functional studies are warranted to validate this association and further investigate our findings.

Keywords

References

  1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015;65:87-108. https://doi.org/10.3322/caac.21262
  2. Rojas K, Stuckey A. Breast cancer epidemiology and risk factors. Clin Obstet Gynecol 2016;59:651-72. https://doi.org/10.1097/GRF.0000000000000239
  3. Blackburn EH. Telomeres and telomerase: the means to the end (Nobel lecture). Angew Chem Int Ed Engl 2010;49:7405-21. https://doi.org/10.1002/anie.201002387
  4. Mathon NF, Lloyd AC. Cell senescence and cancer. Nat Rev Cancer 2001;1:203-13. https://doi.org/10.1038/35106045
  5. Pfeiffer V, Lingner J. Replication of telomeres and the regulation of telomerase. Cold Spring Harb Perspect Biol 2013;5:a010405.
  6. Greider CW. Telomerase activity, cell proliferation, and cancer. Proc Natl Acad Sci U S A 1998;95:90-2. https://doi.org/10.1073/pnas.95.1.90
  7. Telomeres Mendelian Randomization Collaboration, Haycock PC, Burgess S, Nounu A, Zheng J, Okoli GN, et al. Association between telomere length and risk of cancer and non-neoplastic diseases: a Mendelian randomization study. JAMA Oncol 2017;3:636-51. https://doi.org/10.1001/jamaoncol.2016.5945
  8. Zhu X, Han W, Xue W, Zou Y, Xie C, Du J, et al. The association between telomere length and cancer risk in population studies. Sci Rep 2016;6:22243. https://doi.org/10.1038/srep22243
  9. Barwell J, Pangon L, Georgiou A, Docherty Z, Kesterton I, Ball J, et al. Is telomere length in peripheral blood lymphocytes correlated with cancer susceptibility or radiosensitivity? Br J Cancer 2007;97:1696-700. https://doi.org/10.1038/sj.bjc.6604085
  10. De Vivo I, Prescott J, Wong JY, 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. https://doi.org/10.1158/1055-9965.EPI-08-0998
  11. Zheng YL, Ambrosone C, Byrne C, Davis W, Nesline M, McCann SE. Telomere length in blood cells and breast cancer risk: investigations in two case-control studies. Breast Cancer Res Treat 2010;120:769-75. https://doi.org/10.1007/s10549-009-0440-z
  12. Kim S, Sandler DP, Carswell G, De Roo LA, Parks CG, Cawthon R, et al. Telomere length in peripheral blood and breast cancer risk in a prospective case-cohort analysis: results from the Sister Study. Cancer Causes Control 2011;22:1061-6. https://doi.org/10.1007/s10552-011-9778-8
  13. Svenson U, Nordfjall 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. https://doi.org/10.1158/0008-5472.CAN-07-6497
  14. Gramatges MM, Telli ML, Balise R, Ford JM. Longer relative telomere length in blood from women with sporadic and familial breast cancer compared with healthy controls. Cancer Epidemiol Biomarkers Prev 2010;19:605-13. https://doi.org/10.1158/1055-9965.EPI-09-0896
  15. Pellatt AJ, Wolff RK, Torres-Mejia G, John EM, Herrick JS, Lundgreen A, et al. Telomere length, telomere-related genes, and breast cancer risk: the breast cancer health disparities study. Genes Chromosomes Cancer 2013;52:595-609.
  16. Shen J, Terry MB, Gurvich I, Liao Y, Senie RT, Santella RM. Short telomere length and breast cancer risk: a study in sister sets. Cancer Res 2007;67:5538-44. https://doi.org/10.1158/0008-5472.CAN-06-3490
  17. Shen J, Gammon MD, Terry MB, Wang Q, Bradshaw P, Teitelbaum SL, et al. Telomere length, oxidative damage, antioxidants and breast cancer risk. Int J Cancer 2009;124:1637-43. https://doi.org/10.1002/ijc.24105
  18. Pooley KA, Sandhu MS, Tyrer J, Shah M, Driver KE, Luben RN, et al. Telomere length in prospective and retrospective cancer case-control studies. Cancer Res 2010;70:3170-6. https://doi.org/10.1158/0008-5472.CAN-09-4595
  19. Qu S, Wen W, Shu XO, Chow WH, Xiang YB, Wu J, et al. Association of leukocyte telomere length with breast cancer risk: nested case-control findings from the Shanghai Women's Health Study. Am J Epidemiol 2013;177:617-24. https://doi.org/10.1093/aje/kws291
  20. Haiman CA, Chen GK, Vachon CM, Canzian F, Dunning A, Millikan RC, et al. A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer. Nat Genet 2011;43:1210-4. https://doi.org/10.1038/ng.985
  21. Palmer JR, Ruiz-Narvaez EA, Rotimi CN, Cupples LA, Cozier YC, Adams-Campbell LL, et al. Genetic susceptibility loci for subtypes of breast cancer in an African American population. Cancer Epidemiol Biomarkers Prev 2013;22:127-34. https://doi.org/10.1158/1055-9965.EPI-12-0769
  22. Bojesen SE, Pooley KA, Johnatty SE, Beesley J, Michailidou K, Tyrer JP, et al. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. Nat Genet 2013;45:371-84, 384e1-2. https://doi.org/10.1038/ng.2566
  23. Gao L, Thakur A, Liang Y, Zhang S, Wang T, Chen T, et al. Polymorphisms in the TERT gene are associated with lung cancer risk in the Chinese Han population. Eur J Cancer Prev 2014;23:497-501. https://doi.org/10.1097/CEJ.0000000000000086
  24. Li G, Jin TB, Wei XB, He SM, Liang HJ, Yang HX, et al. Selected polymorphisms of GSTP1 and TERT were associated with glioma risk in Han Chinese. Cancer Epidemiol 2012;36:525-7. https://doi.org/10.1016/j.canep.2012.06.008
  25. Cawthon RM. Telomere measurement by quantitative PCR. Nucleic Acids Res 2002;30:e47. https://doi.org/10.1093/nar/30.10.e47
  26. Stewart SA, Weinberg RA. Telomeres: cancer to human aging. Annu Rev Cell Dev Biol 2006;22:531-57. https://doi.org/10.1146/annurev.cellbio.22.010305.104518
  27. Shay JW. Role of telomeres and telomerase in aging and cancer. Cancer Discov 2016;6:584-93. https://doi.org/10.1158/2159-8290.CD-16-0062
  28. 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. https://doi.org/10.1007/s10549-012-2058-9
  29. Rao S, Ye N, Hu H, Shen Y, Xu Q. Variants in TERT influencing telomere length are associated with paranoid schizophrenia risk. Am J Med Genet B Neuropsychiatr Genet 2016;171B:317-24.
  30. Pellatt AJ, Wolff RK, Lundgreen A, Cawthon R, Slattery ML. Genetic and lifestyle influence on telomere length and subsequent risk of colon cancer in a case control study. Int J Mol Epidemiol Genet 2012;3:184-94.

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