Breast Cancer Research and Treatment

, Volume 133, Issue 1, pp 127–135 | Cite as

Physical activity and breast cancer survival: an epigenetic link through reduced methylation of a tumor suppressor gene L3MBTL1

  • Hongmei Zeng
  • Melinda L. Irwin
  • Lingeng Lu
  • Harvey Risch
  • Susan Mayne
  • Lina Mu
  • Qian Deng
  • Luca Scarampi
  • Marco Mitidieri
  • Dionyssios Katsaros
  • Herbert YuEmail author
Preclinical study


The study was conducted to determine the effect of physical activity on DNA methylation and to predict the consequence of this effect concerning gene expression and breast cancer survival. Blood samples, collected from 12 breast cancer patients who participated in a randomized clinical trial of exercise, were examined for exercise-related changes in DNA methylation using a methylation microarray. Tumor samples of 348 breast cancer patients were analyzed with qRT-PCR and qMSP to determine gene expression and methylation identified in the microarray analysis. Cox regression models were developed to predict survival outcomes in association with gene expression and methylation. After 6 months of moderate-intensity aerobic exercise, changes in DNA methylation (P < 5 × 10−5) in peripheral blood leukocytes were detected in 43 genes from a panel of 14 495. Based on the list, we analyzed gene expression in association with overall survival in breast tumors and found three genes whose methylation was reduced after exercise were favorably in association with overall survival, i.e., higher expression associated with better survival. Of the three genes, L3MBTL1 was a putative tumor suppressor gene with known function to repress chromatin for transcription, which is activated mainly in germline stem cells. Further analyses of tumor features among patients indicated that high expression of L3MBTL1 was associated with low grade and hormone receptor–positive tumors, as well as low risk of disease recurrence and breast cancer death. In conclusion, the study suggests that increasing physical activity after a breast cancer diagnosis may affect epigenetic regulation of tumor suppressor genes, which have favorable impacts on survival outcomes of breast cancer patients.


Physical activity Survival DNA methylation L3MBTL1 Tumor suppressor gene 


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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Hongmei Zeng
    • 1
    • 2
  • Melinda L. Irwin
    • 1
  • Lingeng Lu
    • 1
  • Harvey Risch
    • 1
  • Susan Mayne
    • 1
  • Lina Mu
    • 3
  • Qian Deng
    • 1
  • Luca Scarampi
    • 4
  • Marco Mitidieri
    • 4
  • Dionyssios Katsaros
    • 4
  • Herbert Yu
    • 1
    Email author
  1. 1.Department of Epidemiology and Public HealthYale Cancer Center, Yale University School of Public HealthNew HavenUSA
  2. 2.Department of Cancer Epidemiology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education)Peking University School of Oncology, Beijing Cancer Hospital and InstituteBeijingChina
  3. 3.Department of Social and Preventive Medicine, School of Public Health and Health ProfessionsUniversity at Buffalo, The State University of New YorkBuffaloUSA
  4. 4.Department of Obstetrics and Gynecology, Gynecologic Oncology and Breast Cancer UnitUniversity of TurinTurinItaly

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