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Breast Cancer Research and Treatment

, Volume 172, Issue 1, pp 105–112 | Cite as

Randomized controlled trial of weight loss versus usual care on telomere length in women with breast cancer: the lifestyle, exercise, and nutrition (LEAN) study

  • Tara Sanft
  • Ilana Usiskin
  • Maura Harrigan
  • Brenda Cartmel
  • Lingeng Lu
  • Fang-Yong Li
  • Yang Zhou
  • Anees Chagpar
  • Leah M. Ferrucci
  • Lajos Pusztai
  • Melinda L. Irwin
Clinical trial

Abstract

Purpose

Some studies suggest that telomere shortening may be associated with increased breast cancer risk and mortality. Obesity is also associated with increased breast cancer risk and mortality. Few studies have examined changes in telomere length in overweight or obese breast cancer survivors. The purpose of our study was to examine the effect of a 6-month diet- and exercise-induced weight loss intervention versus usual care on telomere length in breast cancer survivors.

Methods

151 breast cancer survivors with body mass index (BMI) ≥ 25 kg/m2 were randomly assigned to a 6-month weight loss intervention (n = 93) or to usual care (n = 58). Fasting blood samples, height, weight, physical activity, and diet were measured at baseline and 6-months. Relative telomere length (RTL) was measured by quantitative-polymerase chain reaction (qPCR) done on buffy coat-extracted genomic DNA. Mean baseline to 6-month changes were compared between groups (intention-to-treat) using generalized estimating equations.

Results

Complete telomere data were available in 125 participants. Women were 58 ± 8 years, with BMI 33.0 ± 6.2 kg/m2 and were 2.9 ± 2.5 years from diagnosis; 90% were non-Hispanic white, and 76% had stage 0/I breast cancer. After 6 months, women randomized to weight loss had 3% telomere lengthening compared to 5% shortening in the usual care group (p = 0.12). Among women with stage 0/I, the intervention group experienced 7% telomere lengthening compared to 8% shortening in the usual care group (p = 0.01). No intervention effect was observed in women with stage II/III breast cancer.

Conclusion

Our findings suggest a weight loss intervention in stage 0 and 1 breast cancer survivors may lead to telomere lengthening, compared to a shortening in their usual care counterparts.

Keywords

Breast cancer Exercise Weight loss Telomere 

Notes

Funding

Supported by American Institute for Cancer Research and in part by a grant from the Breast Cancer Research Foundation. Also supported in part by the Yale Cancer Center Support Grant P30 CA016359 and the Clinical and Translational Science Award Grant Number UL1 TR000142 from the National Center for Advancing Translational Science, a component of the National Institutes of Health.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Lu W, Zhang Y, Liu D et al (2013) Telomeres-structure, function, and regulation. Exp Cell Res 319:133–141CrossRefGoogle Scholar
  2. 2.
    Smogorzewska A, de Lange T (2004) Regulation of telomerase by telomeric proteins. Annu Rev Biochem 73:177–208CrossRefGoogle Scholar
  3. 3.
    McEachern MJ, Krauskopf A, Blackburn EH (2000) Telomeres and their control. Annu Rev Genet 34:331–358CrossRefGoogle Scholar
  4. 4.
    Buxton JL, Suderman M, Pappas JJ et al (2014) Human leukocyte telomere length is associated with DNA methylation levels in multiple subtelomeric and imprinted loci. Sci Rep 4:4954CrossRefGoogle Scholar
  5. 5.
    Risques RA, Vaughan TL, Li X et al (2007) Leukocyte telomere length predicts cancer risk in Barrett’s esophagus. Cancer Epidemiol Biomarkers Prev 16:2649–2655CrossRefGoogle Scholar
  6. 6.
    Mirabello L, Garcia-Closas M, Cawthon R et al (2010) Leukocyte telomere length in a population-based case-control study of ovarian cancer: a pilot study. Cancer Causes Control 21:77–82CrossRefGoogle Scholar
  7. 7.
    Wentzensen IM, Mirabello L, Pfeiffer RM et al (2011) The association of telomere length and cancer: a meta-analysis. Cancer Epidemiol Biomarkers Prev 20:1238–1250CrossRefGoogle Scholar
  8. 8.
    Gramatges MM, Telli ML, Balise R et al (2010) Longer relative telomere length in blood from women with sporadic and familial breast cancer compared with healthy controls. Cancer Epidemiol Biomarkers Prev 19:605–613CrossRefGoogle Scholar
  9. 9.
    De Vivo I, Prescott J, Wong JY et al (2009) A prospective study of relative telomere length and postmenopausal breast cancer risk. Cancer Epidemiol Biomarkers Prev 18:1152–1156CrossRefGoogle Scholar
  10. 10.
    Shen J, Gammon MD, Terry MB et al (2009) Telomere length, oxidative damage, antioxidants and breast cancer risk. Int J Cancer 124:1637–1643CrossRefGoogle Scholar
  11. 11.
    Shen J, Terry MB, Gurvich I et al (2007) Short telomere length and breast cancer risk: a study in sister sets. Cancer Res 67:5538–5544CrossRefGoogle Scholar
  12. 12.
    Ma H, Zhou Z, Wei S et al (2011) Shortened telomere length is associated with increased risk of cancer: a meta-analysis. PLoS ONE 6:e20466CrossRefGoogle Scholar
  13. 13.
    Duggan C, Risques R, Alfano C et al (2014) Change in peripheral blood leukocyte telomere length and mortality in breast cancer survivors. J Natl Cancer Inst 106:dju035CrossRefGoogle Scholar
  14. 14.
    Nordfjall K, Eliasson M, Stegmayr B et al (2008) Telomere length is associated with obesity parameters but with a gender difference. Obesity (Silver Spring) 16:2682–2689CrossRefGoogle Scholar
  15. 15.
    Kim S, Parks CG, DeRoo LA et al (2009) Obesity and weight gain in adulthood and telomere length. Cancer Epidemiol Biomarkers Prev 18:816–820CrossRefGoogle Scholar
  16. 16.
    Muezzinler A, Zaineddin AK, Brenner H (2014) Body mass index and leukocyte telomere length in adults: a systematic review and meta-analysis. Obes Rev 15:192–201CrossRefGoogle Scholar
  17. 17.
    Cui Y, Gao YT, Cai Q et al (2013) Associations of leukocyte telomere length with body anthropometric indices and weight change in Chinese women. Obesity (Silver Spring) 21:2582–2588CrossRefGoogle Scholar
  18. 18.
    Carulli L, Anzivino C, Baldelli E et al (2016) Telomere length elongation after weight loss intervention in obese adults. Mol Genet Metab 118:138–142CrossRefGoogle Scholar
  19. 19.
    Mason C, Risques RA, Xiao L et al (2013) Independent and combined effects of dietary weight loss and exercise on leukocyte telomere length in postmenopausal women. Obesity (Silver Spring) 21:E549–E554CrossRefGoogle Scholar
  20. 20.
    Garcia-Calzon S, Moleres A, Marcos A et al (2014) Telomere length as a biomarker for adiposity changes after a multidisciplinary intervention in overweight/obese adolescents: the EVASYON study. PLoS ONE 9:e89828CrossRefGoogle Scholar
  21. 21.
    Ornish D, Lin J, Chan JM et al (2013) Effect of comprehensive lifestyle changes on telomerase activity and telomere length in men with biopsy-proven low-risk prostate cancer: 5-year follow-up of a descriptive pilot study. Lancet Oncol 14:1112–1120CrossRefGoogle Scholar
  22. 22.
    Harrigan M, Cartmel B, Loftfield E et al (2016) Randomized trial comparing telephone versus in-person weight loss counseling on body composition and circulating biomarkers in women treated for breast cancer: the lifestyle, exercise, and nutrition (LEAN) study. J Clin Oncol 34:669–676CrossRefGoogle Scholar
  23. 23.
    Cawthon RM (2009) Telomere length measurement by a novel monochrome multiplex quantitative PCR method. Nucleic Acids Res 37:e21CrossRefGoogle Scholar
  24. 24.
    Lan Q, Cawthon R, Gao Y et al (2013) Longer telomere length in peripheral white blood cells is associated with risk of lung cancer and the rs2736100 (CLPTM1L-TERT) polymorphism in a prospective cohort study among women in China. PLoS ONE 8:e59230CrossRefGoogle Scholar
  25. 25.
    Ennour-Idrissi K, Maunsell E, Diorio C (2017) Telomere length and breast cancer prognosis: a systematic review. Cancer Epidemiol Biomarkers Prev 26:3–10CrossRefGoogle Scholar
  26. 26.
    Zheng YL, Ambrosone C, Byrne C et al (2010) Telomere length in blood cells and breast cancer risk: investigations in two case-control studies. Breast Cancer Res Treat 120:769–775CrossRefGoogle Scholar
  27. 27.
    Zheng YL, Loffredo CA, Shields PG et al (2009) Chromosome 9 arm-specific telomere length and breast cancer risk. Carcinogenesis 30:1380–1386CrossRefGoogle Scholar
  28. 28.
    Garland SN, Johnson B, Palmer C et al (2014) Physical activity and telomere length in early stage breast cancer survivors. Breast Cancer Res 16:413CrossRefGoogle Scholar
  29. 29.
    Cherkas LF, Hunkin JL, Kato BS et al (2008) The association between physical activity in leisure time and leukocyte telomere length. Arch Intern Med 168:154–158CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Tara Sanft
    • 1
  • Ilana Usiskin
    • 1
  • Maura Harrigan
    • 2
  • Brenda Cartmel
    • 1
    • 2
  • Lingeng Lu
    • 2
  • Fang-Yong Li
    • 2
  • Yang Zhou
    • 1
  • Anees Chagpar
    • 1
  • Leah M. Ferrucci
    • 2
  • Lajos Pusztai
    • 1
  • Melinda L. Irwin
    • 1
    • 2
  1. 1.Yale Cancer CenterYale University School of MedicineNew HavenUSA
  2. 2.Yale School of Public Health, Yale Cancer CenterYale University School of MedicineNew HavenUSA

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