The Effects of Soy Supplementation on Gene Express
2016-08-26 15:39阅读：
伊利诺大学医学院-神经内科-主治医师
新浪博客
,
Methods Women (n = 140) with early-stage breast cancer were randomly assigned to soy protein supplementation (n = 70) or placebo (n = 70) for 7 to 30 days, from diagnosis until surgery. Adherence was determined by plasma isoflavones: genistein and daidzein. Gene expression changes were evaluated by NanoString in pre- and posttreatment tumor tissue. Genome-wide expression analysis was performed on posttreatment tissue. Proliferation (Ki67) and apoptosis (Cas3) were assessed by immunohistochemistry.
Results Plasma isoflavones rose in the soy group (two-sided Wilcoxon rank-sum test, P < .001) and did not change in the placebo group. In paired analysis of pre- and posttreatment samples, 21 genes (out of 202) showed altered expression_r(two-sided Student’s t-test, P < .05). Several genes including FANCC and UGT2A1 revealed different magnitude and direction of expression changes between the two groups (two-sided Student’s t-test, P < .05). A high-genistein signature consisting of 126 differentially expressed genes was identified from microarray analysis of tumors. This signature was characterized by overexpression_r(>2-fold) of cell cycle transcripts, including those that promote cell proliferation, such as FGFR2, E2F5, BUB1, CCNB2, MYBL2, CDK1, and CDC20 (P < .01). Soy intake did not result in statistically significant changes in Ki67 or Cas3.
Conclusions Gene expression associated with soy intake and high plasma genistein defines a signature characterized by overexpression of FGFR2 and genes that drive cell cycle and proliferation pathways. These findings raise the concerns that in a subset of women soy could adversely affect gene expression in breast cancer.
Memo to the Media: Soy Supplementation Adversely Effects Expression of Breast Cancer-Related Genes JNCI J Natl Cancer Inst(2014) 106 (9): dju313 doi:10.1093/jnci/dju313 First published online September 4, 2014 (1 pages)
- Lianne Russo,
- Rafael Cabal,
- Jorge S. Reis-Filho,
- William Gerald†,
- Hiram Cody,
- Raya Khanin,
- Jacqueline Bromberg and
- Larry Norton
- Author Affiliations
- Affiliations of authors: Department of Medicine (MS, AD, LR, JB, LN) and Department of Pathology (RC, JRF, WG) and Department of Surgery (HC) and Department of Computational Biology (RK), Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College (MS, JRF, WG, HC, JB, LN).
- ↵† Deceased.
- Correspondence
to:
Moshe Shike, MD, MSKCC, 1275 York Avenue box 224, New York, NY 10065 (e-mail: shikem@mskcc.org).
- Received February 6, 2014.
- Revision received May 22, 2014.
- Accepted May 28, 2014.
Abstract
Background There are conflicting reports on the impact of soy on breast carcinogenesis. This study examines the effects of soy supplementation on breast cancer-related genes and pathways.Methods Women (n = 140) with early-stage breast cancer were randomly assigned to soy protein supplementation (n = 70) or placebo (n = 70) for 7 to 30 days, from diagnosis until surgery. Adherence was determined by plasma isoflavones: genistein and daidzein. Gene expression changes were evaluated by NanoString in pre- and posttreatment tumor tissue. Genome-wide expression analysis was performed on posttreatment tissue. Proliferation (Ki67) and apoptosis (Cas3) were assessed by immunohistochemistry.
Results Plasma isoflavones rose in the soy group (two-sided Wilcoxon rank-sum test, P < .001) and did not change in the placebo group. In paired analysis of pre- and posttreatment samples, 21 genes (out of 202) showed altered expression_r(two-sided Student’s t-test, P < .05). Several genes including FANCC and UGT2A1 revealed different magnitude and direction of expression changes between the two groups (two-sided Student’s t-test, P < .05). A high-genistein signature consisting of 126 differentially expressed genes was identified from microarray analysis of tumors. This signature was characterized by overexpression_r(>2-fold) of cell cycle transcripts, including those that promote cell proliferation, such as FGFR2, E2F5, BUB1, CCNB2, MYBL2, CDK1, and CDC20 (P < .01). Soy intake did not result in statistically significant changes in Ki67 or Cas3.
Conclusions Gene expression associated with soy intake and high plasma genistein defines a signature characterized by overexpression of FGFR2 and genes that drive cell cycle and proliferation pathways. These findings raise the concerns that in a subset of women soy could adversely affect gene expression in breast cancer.
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Solicited Editorial:- V. Craig Jordan
Memo to the Media: Soy Supplementation Adversely Effects Expression of Breast Cancer-Related Genes JNCI J Natl Cancer Inst(2014) 106 (9): dju313 doi:10.1093/jnci/dju313 First published online September 4, 2014 (1 pages)
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