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J Natl Cancer Inst. 2014 Sep 4;106(9). pii: dju189. doi: 10.1093/jnci/dju189. Print 2014 Sep.

The effects of soy supplementation on gene expression in breast cancer: a randomized placebo-controlled study.

Author information

1
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). shikem@mskcc.org.
2
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).

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 (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 (>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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00597532.

PMID:
25190728
PMCID:
PMC4817128
DOI:
10.1093/jnci/dju189
[Indexed for MEDLINE]
Free PMC Article

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