Abstract
Objective
Telomeres are required for maintaining genomic integrity and may play a role in carcinogenesis. Some, but not all, epidemiologic studies have found that short telomeres in leukocytes are associated with an increased risk of breast cancer. To further elucidate this potential association, we examined telomere length in relation to breast cancer risk in prospectively collected blood samples from the Sister Study, a cohort of women aged 35–74 years who have a sister with breast cancer.
Methods
We performed a case-cohort analysis comparing incident breast cancer cases (n = 342) with a subcohort (n = 735), randomly selected from 29,026 participants, enrolled by June 1, 2007. Relative telomere length in peripheral blood cells was estimated using a single-tube monochrome multiplex quantitative PCR assay.
Results
No association was observed between telomere length and breast cancer risk. Compared with the longest quartile, hazard ratios (HR) associated with the second, third, and the shortest quartile were 0.91 [95% confidence interval (95% CI): 0.62–1.34], 1.11 (95% CI: 0.77–1.60), and 0.93 (95% CI: 0.64–1.35), respectively. Subgroup analyses by menopausal status, invasiveness, or estrogen receptor status of breast cancer did not reveal evidence of association between telomere length in blood cells and subsequent breast cancer risk.
Conclusions
This prospective investigation does not support telomere length in blood cells as a biomarker for breast cancer risk.
References
Monaghan P, Haussmann MF (2006) Do telomere dynamics link lifestyle and lifespan? Trends Ecol Evol 21(1):47–53
Meeker AK, Hicks JL, Gabrielson E, Strauss WM, De Marzo AM, Argani P (2004) Telomere shortening occurs in subsets of normal breast epithelium as well as in situ and invasive carcinoma. Am J Pathol 164(3):925–935
Cheung AL, Deng W (2008) Telomere dysfunction, genome instability and cancer. Front Biosci 13:2075–2090
Sharpless NE, DePinho RA (2004) Telomeres, stem cells, senescence, and cancer. J Clin Invest 113(2):160–168
Chin K, de Solorzano CO, Knowles D, Jones A, Chou W, Rodriguez EG et al (2004) In situ analyses of genome instability in breast cancer. Nat Genet 36(9):984–988
Meeker AK, Hicks JL, Gabrielson E, Strauss WM, De Marzo AM, Argani P (2004) Telomere shortening occurs in subsets of normal breast epithelium as well as in situ and invasive carcinoma. Am J Pathol 164(3):925–935
Levy T, Agoulnik I, Atkinson EN, Tong XW, Gause HM, Hasenburg A et al (1998) Telomere length in human white blood cells remains constant with age and is shorter in breast cancer patients. Anticancer Res 18(3A):1345–1349
Pooley KA, Sandhu MS, Tyrer J, Shah M, Driver KE, Luben RN et al (2010) Telomere length in prospective and retrospective cancer case–control studies. Cancer Res 70(8):3170–3176
Shen J, Gammon MD, Terry MB, Wang Q, Bradshaw P, Teitelbaum SL et al (2009) Telomere length, oxidative damage, antioxidants and breast cancer risk. Int J Cancer 124(7):1637–1643
Svenson U, Nordfjall K, Stegmayr B, Manjer J, Nilsson P, Tavelin B et al (2008) Breast cancer survival is associated with telomere length in peripheral blood cells. Cancer Res 68(10):3618–3623
Gramatges MM, Telli ML, Balise R, Ford JM (2010) Longer relative telomere length in blood from women with sporadic and familial breast cancer compared with healthy controls. Cancer Epidemiol Biomarkers Prev 19(2):605–613
Zheng YL, Ambrosone C, Byrne C, Davis W, Nesline M, McCann SE (2010) Telomere length in blood cells and breast cancer risk: investigations in two case–control studies. Breast Cancer Res Treat 120(3):769–775
De Vivo I, Prescott J, Wong JY, Kraft P, Hankinson SE, Hunter DJ (2009) A prospective study of relative telomere length and postmenopausal breast cancer risk. Cancer Epidemiol Biomarkers Prev 18(4):1152–1156
Weinberg CR, Shore DL, Umbach DM, Sandler DP (2007) Using risk-based sampling to enrich cohorts for endpoints, genes, and exposures. Am J Epidemiol 166(4):447–455
Cawthon RM (2009) Telomere length measurement by a novel monochrome multiplex quantitative PCR method. Nucleic Acids Res 37(3):e21
Prentice RL (1986) A case-cohort design for epidemiologic cohort studies and disease prevention trials. Biometrika 73(1):1–11
Barlow WE, Ichikawa L, Rosner D, Izumi S (1999) Analysis of case-cohort designs. J Clin Epidemiol 52(12):1165–1172
Shen J, Terry MB, Gurvich I, Liao Y, Senie RT, Santella RM (2007) Short telomere length and breast cancer risk: a study in sister sets. Cancer Res 67(11):5538–5544
Schröder CP, Wisman GB, de Jong S, van der Graaf WT, Ruiters MH, Mulder NH et al (2001) Telomere length in breast cancer patients before and after chemotherapy with or without stem cell transplantation. Br J Cancer 84(10):1348–1353
Mirabello L, Yu K, Kraft P, De Vivo I, Hunter DJ, Prescott J et al (2010) The association of telomere length and genetic variation in telomere biology genes. Hum Mutat 31(9):1050–1058
Cawthon RM (2002) Telomere measurement by quantitative PCR. Nucleic Acids Res 30(10):e47
Valdes AM, Andrew T, Gardner JP, Kimura M, Oelsner E, Cherkas LF et al (2005) Obesity, cigarette smoking, and telomere length in women. Lancet 366(9486):662–664
Kim S, Parks CG, DeRoo LA, Chen H, Taylor JA, Cawthon RM et al (2009) Obesity and weight gain in adulthood and telomere length. Cancer Epidemiol Biomarkers Prev 18(3):816–820
Acknowledgments
This research was supported by the Intramural Program of the National Institutes of Health, National Institute of Environmental Health Sciences (Z01 ES044005 and Z01 ES049033). Authors are grateful for technical support received from the Molecular Genetics Core Facility at NIEHS.
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Kim, S., Sandler, D.P., Carswell, G. 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 22, 1061–1066 (2011). https://doi.org/10.1007/s10552-011-9778-8
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DOI: https://doi.org/10.1007/s10552-011-9778-8