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学科主题: 临床医学
题名:
Physical activity and breast cancer survival: an epigenetic link through reduced methylation of a tumor suppressor gene L3MBTL1
作者: Zeng, Hongmei1,2; Irwin, Melinda L.1; Lu, Lingeng1; Risch, Harvey1; Mayne, Susan1; Mu, Lina3; Deng, Qian1; Scarampi, Luca4; Mitidieri, Marco4; Katsaros, Dionyssios4; Yu, Herbert1
关键词: Physical activity ; Survival ; DNA methylation ; L3MBTL1 ; Tumor suppressor gene
刊名: BREAST CANCER RESEARCH AND TREATMENT
发表日期: 2012-05-01
DOI: 10.1007/s10549-011-1716-7
卷: 133, 期:1, 页:127-135
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: RANDOMIZED CONTROLLED-TRIAL ; POSTMENOPAUSAL WOMEN ; FASTING INSULIN ; CLINICAL-TRIAL ; GROWTH-FACTORS ; YALE EXERCISE ; EXPRESSION ; HYPERMETHYLATION ; SURVIVORSHIP ; PROGRESSION
英文摘要:

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 x 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.

语种: 英语
WOS记录号: WOS:000303509200012
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61866
Appears in Collections:北京大学临床肿瘤学院_期刊论文

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作者单位: 1.Yale Univ, Sch Publ Hlth, Yale Canc Ctr, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA
2.Peking Univ, Sch Oncol, Beijing Canc Hosp & Inst,Minist Educ, Dept Canc Epidemiol,Key Lab Carcinogenesis & Tran, Beijing 100871, Peoples R China
3.SUNY Buffalo, Dept Social & Prevent Med, Sch Publ Hlth & Hlth Profess, Buffalo, NY 14214 USA
4.Univ Turin, Dept Obstet & Gynecol, Gynecol Oncol & Breast Canc Unit, Turin, Italy

Recommended Citation:
Zeng, Hongmei,Irwin, Melinda L.,Lu, Lingeng,et al. Physical activity and breast cancer survival: an epigenetic link through reduced methylation of a tumor suppressor gene L3MBTL1[J]. BREAST CANCER RESEARCH AND TREATMENT,2012,133(1):127-135.
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