Skip to main content

Advertisement

SpringerLink
Log in

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

  • Clinical trial
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

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.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Lu W, Zhang Y, Liu D et al (2013) Telomeres-structure, function, and regulation. Exp Cell Res 319:133–141

    Article  CAS  Google Scholar 

  2. Smogorzewska A, de Lange T (2004) Regulation of telomerase by telomeric proteins. Annu Rev Biochem 73:177–208

    Article  CAS  Google Scholar 

  3. McEachern MJ, Krauskopf A, Blackburn EH (2000) Telomeres and their control. Annu Rev Genet 34:331–358

    Article  CAS  Google Scholar 

  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 4:4954

    Article  CAS  Google Scholar 

  5. Risques RA, Vaughan TL, Li X et al (2007) Leukocyte telomere length predicts cancer risk in Barrett’s esophagus. Cancer Epidemiol Biomarkers Prev 16:2649–2655

    Article  CAS  Google Scholar 

  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 21:77–82

    Article  Google Scholar 

  7. Wentzensen IM, Mirabello L, Pfeiffer RM et al (2011) The association of telomere length and cancer: a meta-analysis. Cancer Epidemiol Biomarkers Prev 20:1238–1250

    Article  CAS  Google Scholar 

  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 19:605–613

    Article  CAS  Google Scholar 

  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 18:1152–1156

    Article  Google Scholar 

  10. Shen J, Gammon MD, Terry MB et al (2009) Telomere length, oxidative damage, antioxidants and breast cancer risk. Int J Cancer 124:1637–1643

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  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:e20466

    Article  CAS  Google Scholar 

  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:dju035

    Article  Google Scholar 

  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) 16:2682–2689

    Article  Google Scholar 

  15. Kim S, Parks CG, DeRoo LA et al (2009) Obesity and weight gain in adulthood and telomere length. Cancer Epidemiol Biomarkers Prev 18:816–820

    Article  CAS  Google Scholar 

  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 15:192–201

    Article  CAS  Google Scholar 

  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) 21:2582–2588

    Article  Google Scholar 

  18. Carulli L, Anzivino C, Baldelli E et al (2016) Telomere length elongation after weight loss intervention in obese adults. Mol Genet Metab 118:138–142

    Article  CAS  Google Scholar 

  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–E554

    Article  Google Scholar 

  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:e89828

    Article  Google Scholar 

  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 14:1112–1120

    Article  CAS  Google Scholar 

  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 34:669–676

    Article  Google Scholar 

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

    Article  Google Scholar 

  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:e59230

    Article  CAS  Google Scholar 

  25. Ennour-Idrissi K, Maunsell E, Diorio C (2017) Telomere length and breast cancer prognosis: a systematic review. Cancer Epidemiol Biomarkers Prev 26:3–10

    Article  CAS  Google Scholar 

  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 120:769–775

    Article  Google Scholar 

  27. Zheng YL, Loffredo CA, Shields PG et al (2009) Chromosome 9 arm-specific telomere length and breast cancer risk. Carcinogenesis 30:1380–1386

    Article  CAS  Google Scholar 

  28. Garland SN, Johnson B, Palmer C et al (2014) Physical activity and telomere length in early stage breast cancer survivors. Breast Cancer Res 16:413

    Article  Google Scholar 

  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 168:154–158

    Article  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Yale Cancer Center, Yale University School of Medicine, 333 Cedar St, PO Box 208032, New Haven, CT, 06520-8032, USA

    Tara Sanft, Ilana Usiskin, Brenda Cartmel, Yang Zhou, Anees Chagpar, Lajos Pusztai & Melinda L. Irwin

  2. Yale School of Public Health, Yale Cancer Center, Yale University School of Medicine, New Haven, CT, USA

    Maura Harrigan, Brenda Cartmel, Lingeng Lu, Fang-Yong Li, Leah M. Ferrucci & Melinda L. Irwin

Authors
  1. Tara Sanft
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ilana Usiskin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maura Harrigan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Brenda Cartmel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lingeng Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fang-Yong Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yang Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Anees Chagpar
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Leah M. Ferrucci
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Lajos Pusztai
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Melinda L. Irwin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tara Sanft.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sanft, T., Usiskin, I., Harrigan, M. et al. Randomized controlled trial of weight loss versus usual care on telomere length in women with breast cancer: the lifestyle, exercise, and nutrition (LEAN) study. Breast Cancer Res Treat 172, 105–112 (2018). https://doi.org/10.1007/s10549-018-4895-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-018-4895-7

Keywords

Search

Navigation