Journal of the National Cancer Institute, 2014, 106(9).

The effects of Soy Supplementation on Gene expression in Breast cancer: A randomized Placebo-controlled Study

Moshe Shike, Ashley Stephen Doane, Lianne Russo, et al

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)

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.

美国《国家癌症研究所杂志》，2014年9月

大豆补充剂对乳腺癌细胞基因表达的影响︰ 一项随机双盲安慰剂对照研究

摩西  施克，阿什利 斯蒂芬 杜恩，莉安娜 罗素，等

纪念斯隆-凯特琳癌症中心和威尔康奈尔医学院医学系、病理学系、外科和计算生物学系

背景︰

关于大豆对乳房癌的影响的报道相互矛盾。本研究测试了大豆补充剂对乳腺癌相关基因和通路的影响。

方法︰

患有早期乳腺癌的妇女 (n = 140)被随机分配到大豆补充蛋白 组(n = 70) 或安慰剂组 (n = 70)  7 到 30 天，从确诊直到手术。由等离子体异黄酮测试︰ 金雀异黄素和大豆黄酮。通过纳米牵引技术在处理前和处理后的肿瘤组织中测试基因表达的变化。对治疗后的组织进行全基因组表达分析。通过免疫组织化学法评估 (Ki67) 的增殖和(Cas3)的凋亡。

结果︰

大豆组的血浆异黄酮升高 (双面秩和检验，P <.001) 而在安慰剂组没有改变。处理前和处理后样品的配对分析， 21 对基因（超出202)表现出改变的表达(双边学生 t-检验，P <.05)。包括 FANCC 和 UGT2A1 的几种基因表明两组之间不同量级和方向表达的变化 (双边学生 t-检验，P <.05 )。高-金雀异黄素标记组成的 126 个不同表达的基因被微阵列肿瘤分析确认。 此标记以表达细胞周期转录的过表达(> 2 倍)为特征，其中包括促进细胞增殖，例如 FGFR2、 E2F5、 BUB1、 CCNB2、 MYBL2、 CDK1 和 CDC20 (P <.01)。大豆的摄入量不会造成 Ki67 或 Cas3 的显著变化。

结论︰

与大豆摄入量和高血浆金雀异黄素相关的基因表达定义了由FGFR2 过表达定性的标记，以及驱动细胞周期和扩散途径的基因。这些研究结果令人忧虑，在妇女的子集大豆可能不利于影响基因在乳腺癌中的表达。