Soy Intake May Adversely Affect Gene Expression in Early Breast Cancer
In a randomized study reported in the Journal of the National Cancer Institute, Shike et al found that soy supplementation resulting in high genistein levels was associated with overexpression of the tumorigenic growth factor receptor FGFR2 and genes that drive cell cycle and proliferation pathways.
Study Details
In the study, 140 women with early-stage breast cancer were randomly assigned to receive soy protein supplementation (25.8 g soy protein powder twice a day, n = 70) or placebo (25.8 g milk protein twice a day, n = 70) for 7 to 30 days from diagnosis until surgery. Adherence was determined by the plasma isoflavones genistein and daidzein, the major phytoestrogens of soy. Gene expression changes were evaluated by NanoString in pre- and post-treatment tumor samples. Genome-wide expression analysis was performed on post-treatment samples, and proliferation (Ki67) and apoptosis (Cas3) were measured by immunohistochemistry.
Differential Expression
Plasma isoflavone levels increased in the soy group (P < .001) and did not change in the placebo group. In paired analysis of pre- and post-treatment samples, 21 genes out of 202 examined showed altered expression (all P < .05). Several genes exhibited different magnitude and direction of expression changes in the two groups. For example, expression of FANCC and UGT2A1 increased in 87.5% of tumors in the soy group and decreased in the control group.
Analysis by Genistein Level
On the hypothesis that genistein plasma levels, rather than assignment to the soy group, might be a more accurate marker of genistein effects on gene expression, differential expression was examined according to high plasma genistein level. Median genistein concentration in the soy group was 6.3 ng/mL, and 25% had very low levels (< 0.5 ng/mL); the cutoff for high genistein level was set at > 16 ng/mL, corresponding to the 95th percentile concentration in the placebo group. A high-genistein signature consisting of 126 differentially expressed genes was identified, including 47 overexpressed and 79 underexpressed genes. This signature was characterized by greater than twofold overexpression of cell cycle transcripts, including overexpression of genes that promote cell proliferation, such as FGFR2, E2F5, BUB1, CCNB2, MYBL2, CDK1, and CDC20 (all P < .01). Soy intake was not associated with significant changes in Ki67 or Cas3.
The investigators concluded: “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.”
Moshe Shike, MD, of Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of the National Cancer Institute article.
The study was supported by a grant from the Breast Cancer Research Foundation. The study authors reported no potential conflicts of interest.
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