Soy Foods: Towards the Development of Novel Therapeutics for Breast Cancer

  • Rosalia C. M. Simmen
  • Omar M. Rahal
  • Maria Theresa E. Montales
  • John Mark P. Pabona
  • Melissa E. Heard
  • Ahmed Al-Dwairi
  • Adam R. Brown
  • Frank A. Simmen
Chapter
Part of the Evidence-based Anticancer Complementary and Alternative Medicine book series (ACAM, volume 5)

Abstract

The increasing cognizance that diet (and lifestyle) can modify breast cancer risk and progression has motivated many breast cancer patients to take increasing personal control of the direction of their therapies after diagnosis and surgery. While this has certain advantages, including higher compliance to prescribed drugs and improvements in emotional and mental well-being, it predicates the need for increased understanding of the benefits of particular diets and dietary regimen to the treatment programs and for improved translation of data obtained from studies with animal models into clinical settings. Epidemiological studies have linked high consumption of soy-rich foods to the lower incidence of breast cancer in Asia relative to that in Western countries. The potential of soy-rich foods as breast cancer protective when dietary exposure occurs early in life, has resulted in driving the use of soy and its associated bioactive components, specifically the isoflavone genistein, as chemopreventive agents or as adjuvants to conventional drug therapies. Bioactive components in soy foods may affect hormone and non-hormone-mediated mechanisms. However, their overall biological outcomes remain not well-understood and at times, contradictory, due to distinct physiological contexts and doses of exposure, multiple targets, and inconsistent measures of relevant endpoints. Here we provide an argument in support of the potential use of soy foods for breast cancer patients based on the review of the current literature as well as raise caveats that must be addressed for its successful application as standard-of-care treatment.

Keywords

Breast Cancer Breast Cancer Patient Mammary Gland Breast Cancer Risk Mammary Epithelial Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

Work from our laboratories described in this chapter was supported in part by grants from the United States Department of Agriculture-CRIS 6251-5100002, the Department of Defense Breast Cancer Research Program (CDMRP W81XWH-08-0548), the University of Arkansas for Medical Sciences-Translational Research Institute (UL1 RR0298884), and the National Institutes of Health/National Cancer Institute (CA136493). The authors apologize to the many authors of excellent publications on this topic that could not be cited due to space limitations.

References

  1. Ablett MP, Singh JK, Clarke RB (2012) Stem cells in breast tumours: are they ready for the clinic? Eur J Cancer 48:2104–2116PubMedGoogle Scholar
  2. Adams KF, Lampe PD, Newton KM, Ylvisaker JT, Feld A, Myerson D et al (2005) Soy protein containing isoflavones does not decrease epithelial cell proliferation in a randomized control trial. Am J Clin Nutr 82:620–626PubMedGoogle Scholar
  3. Barker DJ (2007) The origins of the developmental origins theory. J Intern Med 261:412–417PubMedGoogle Scholar
  4. Berner C, Aurmüller E, Gnauck A, Nestelberger M, Just A, Haslberger AG (2010) Epigenetic control of estrogen receptor expression and tumor suppressor genes is modulated by bioactive food components. Ann Nutr Metab 57:183–189PubMedGoogle Scholar
  5. Blackburn GL, Copeland T, Khaodhiar L, Buckley RB (2003) Diet and breast cancer. J Womens Health 12:183–192Google Scholar
  6. Bosviel R, Dumollard E, Déchelotte P, Bignon YJ, Bernard-Gallon D (2012) Can soy phytoestrogens decrease DNA methylation in BRCA1 and BRCA2 oncosuppressor genes in breast cancer? OMICS 16:235–244PubMedGoogle Scholar
  7. Boué SM, Tilghman SL, Eliot S, Zimmerman MC, Williams KY, Payton-Stewart F et al (2009) Identification of glycinol in elicited soybean (Glycine Max). Endocrinology 150:2446–2453PubMedGoogle Scholar
  8. Brennan SF, Cantwell MM, Cardwell CR, Velentzis LS, Woodside JV (2010) Dietary patterns and breast cancer risk. Am J Clin Nutr 91:1294–1302PubMedGoogle Scholar
  9. Caan BJ, Natarajan L, Parker B, Gold EB, Thomson C, Newman V et al (2011) Soy food consumption and breast cancer prognosis. Cancer Epidemiol Biomarkers Prev 20:854–858PubMedGoogle Scholar
  10. Colli JL, Amling CL (2009) Chemoprevention of prostate cancer: what can be recommended to patients? Curr Urol Rep 10:165–171PubMedGoogle Scholar
  11. Conklin M, Keely P (2012) Why the stroma matters in breast cancer: insights into breast cancer patient outcomes through the examination of stromal biomarkers. Cell Adhes Migr 6:249–260Google Scholar
  12. Constantinous AI, White BE, Tonetti D, Yang Y, Liang W, Li W et al (2005) The soy isoflavone daidzein improves the capacity of tamoxifen to prevent mammary tumours. Eur J Cancer 41:647–654Google Scholar
  13. Creighton CJ, Sada YH, Zhang Y, Tsimelzon A, Wong H, Dave B et al (2012) A gene transcription signature of obesity in breast cancer. Breast Cancer Res Treat 132:993–1000PubMedGoogle Scholar
  14. Dagdemir A, Durif J, Ngollo M, Bignon YJ, Bernard-Gallon D (2013) Histone lysine trimethylation or acetylation can be modulated by phytoestrogen, estrogen or anti-HDAC in breast cancer cell lines. Epigenomics 5:51–63Google Scholar
  15. Damonte P, Hodgson JG, Chen JQ, Young LJ, Cardiff RD, Borowsky AD (2008) Mammary carcinoma behavior is programmed in the precancer stem cell. Breast Cancer Res 10:R50PubMedGoogle Scholar
  16. Dave B, Eason RR, Till SR, Geng Y, Velarde MC, Badger TM et al (2005) The soy isoflavone genistein promotes apoptosis in mammary epithelial cells by inducing the tumor suppressor PTEN. Carcinogenesis 26:1793–1803PubMedGoogle Scholar
  17. Day JK, Bauer AM, DesBordes C, Zhuang Y, Kim BE, Newman LG et al (2002) Genistein alters methylation patterns in mice. J Nutr 132(Suppl 8):2419S–2423SPubMedGoogle Scholar
  18. Dia VP, Mejia EG (2010) Lunasin promotes apoptosis in human colon cancer cells by mitochondrial pathway activation and induction of nuclear clusterin expression. Cancer Lett 295:44–53PubMedGoogle Scholar
  19. Dijkstra SC, Lampe JW, Ray RM, Brown R, Wu C, Chen C et al (2010) Biomarkers of dietary exposure are associated with lower risk of breast fibroadenomas in Chinese women. J Nutr 140:1302–1310PubMedGoogle Scholar
  20. Dong JY, Qin LQ (2011) Soy isoflavones consumption and risk of breast cancer incidence or recurrence: a meta-analysis of prospective studies. Breast Cancer Res Treat 125:315–323PubMedGoogle Scholar
  21. Du M, Yang X, Hartman JA, Cooke PS, Doerge DR, Ju YH et al (2012) Low-dose dietary genistein negates the therapeutic effect of tamoxifen in athymic nude mice. Carcinogenesis 33:895–901PubMedGoogle Scholar
  22. Duncan AM, Merz BE, Xu X, Nagel TC, Phipps WR, Kurzer MS (1999) Soy isoflavones exert modest hormonal effects in premenpausal women. J Clin Endocrinol Metab 84:192–197PubMedGoogle Scholar
  23. Fersching DM, Nagel D, Siegele B, Salat C, Heinemann V, Holdenrieder S et al (2012) Apoptosis-related biomarkers sFAS, MIF, ICAM-1 and PAI-1 in serum of breast cancer patients undergoing neoadjuvant chemotherapy. Anticancer Res 32:2047–2058PubMedGoogle Scholar
  24. Galvez AF, de Lumen BO (1999) A soybean cDNA encoding a chromatin-binding peptide inhibits mitosis of mammalian cells. Nat Biotechnol 17:495–500PubMedGoogle Scholar
  25. Galvez AF, Chen N, Macasieb J, de Lumen BO (2001) Chemopreventive property of a soybean peptide (Lunasin) that binds to deacetylated histones and inhibits acetylation. Cancer Res 61:7473–7478PubMedGoogle Scholar
  26. Gann PH, Kazer R, Chatterton R, Gapstur S, Thedford K, Helenowski I et al (2005) Sequential, randomized trial of a low-fat, high-fiber diet and soy supplementation: effects on circulating IGF-I and its binding proteins in premenopausal women. Int J Cancer 116:297–303PubMedGoogle Scholar
  27. Guha N, Kwan ML, Quesenberry CP Jr, Weltzien EK, Castillo AL, Caan BJ (2009) Soy isoflavones and risk of cancer recurrence in a cohort of breast cancer survivors: the Life After Cancer Epidemiology study. Breast Cancer Res Treat 118:395–405PubMedGoogle Scholar
  28. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674PubMedGoogle Scholar
  29. Hennighausen L, Robinson GW (2001) Signaling pathways in mammary gland development. Dev Cell 1:467–475PubMedGoogle Scholar
  30. Hilakivi-Clarke L, De Assis S (2006) Fetal origins of breast cancer. Trends Endocrinol Metab 17:340–348PubMedGoogle Scholar
  31. Hilakivi-Clarke L, Andrade JE, Helferich W (2010) Is soy consumption good or bad for the breast? J Nutr 140:2326S–2334SPubMedGoogle Scholar
  32. Hooper L, Madhavan G, Tice JA, Leinster SJ, Cassidy A (2010) Effects of isoflavones on breast density in pre- and post-menopausal women: a systematic review and meta-analysis of randomized controlled trials. Hum Reprod Update 16:745–760PubMedGoogle Scholar
  33. Hortobagyi GN, de la Garza SJ, Pritchard K, Amadori D, Haidinger R, Hudis CA et al (2005) The global breast cancer burden: variations in epidemiology and survival. Clin Breast Cancer 6:391–401PubMedGoogle Scholar
  34. Howard TD, Ho SM, Zhang L, Chen J, Cui W, Slager R et al (2011) Epigenetic changes with dietary soy in cynomolgus monkeys. PLoS One 6:e26791PubMedGoogle Scholar
  35. Hsieh CC, Hernάndez-Ledesma B, Jeong HJ, Park JH, de Lumen BO (2010a) Complementary roles in cancer prevention: protease inhibitor makes the cancer preventive peptide lunasin bioavailable. PLoS One 5:e8890PubMedGoogle Scholar
  36. Hsieh CC, Hernάndez-Ledesma B, de Lumen BO (2010b) Lunasin, a novel seed peptide, sensitizes human breast cancer MDA-MB231 cells to aspirin-arrested cell cycle and induced apoptosis. Chem Biol Interact 18:127–134Google Scholar
  37. Jeong HJ, Jeong JB, Kim DS, de Lumen BO (2007) Inhibition of core histone acetylation by the cancer preventive peptide lunasin. J Agric Food Chem 55:632–637PubMedGoogle Scholar
  38. Jeong HJ, Jeong JB, Hsieh CC, Hernάndez-Ledesma B, de Lumen BO (2010) Lunasin is present in barley and is bioavailable and bioactive in in vivo and in vitro studies. Nutr Cancer 62:1113–1119PubMedGoogle Scholar
  39. Jeschke J, Van Neste L, Glöckner SC, Dhir M, Calmon MF, Deregowski V et al (2012) Biomarkers for detection and prognosis of breast cancer identified by a functional hypermethylome screen. Epigenetics 7:701–709PubMedGoogle Scholar
  40. Kang JH, Han IH, Sung MK, Yoo H, Kim YG, Kim JS et al (2008) Soyben saponin inhibits tumor cell metastasis by modulating expressions of MMP-2, MMP-9 and TIMP-2. Cancer Lett 261:84–92PubMedGoogle Scholar
  41. Kang X, Zhang Q, Wang S, Huang X, Jin S (2010) Effect of soy isoflavones on breast cancer recurrence and death for patients receiving adjuvant endocrine therapy. CMAJ 182:1857–1862PubMedGoogle Scholar
  42. Kang HB, Zhang YE, Yang JD, Lu KL (2012) Study on soy isoflavone consumption and risk of breast cancer and survival. Asian Pac J Cancer 13:995–998Google Scholar
  43. Khan SA, Chatterton RT, Michel N, Bryk M, Lee O, Ivancic D et al (2012) Soy isoflavone supplementation for breast cancer risk reduction: a randomized phase II trial. Cancer Prev Res 5:309–319Google Scholar
  44. Korde LA, Wu AH, Fears T, Nomura AM, West DW, Kolonel LN et al (2009) Childhood soy intake and breast cancer risk in Asian American women. Cancer Epidemiol Biomarkers Prev 18:1050–1059PubMedGoogle Scholar
  45. Lamartiniere CA (2002) Timing of exposure and mammary cancer risk. J Mammary Gland Biol Neoplasia 7:67–76PubMedGoogle Scholar
  46. Lee SA, Shu XO, Li H, Yang G, Cai H, Wen W et al (2009) Adolescent and adult soy food intake and breast cancer risk: results from the Shanghai women’s health study. Am J Clin Nutr 89:1920–1926PubMedGoogle Scholar
  47. Li G, Robinson GW, Lesche R, Martinez-Diaz H, Jiang Z, Rozengurt N et al (2002) Conditional loss of PTEN leads to precocious development and neoplasia in the mammary gland. Development 129:4159–4170PubMedGoogle Scholar
  48. Lin SY, Xia W, Wang JC, Kwong KY, Spohn B, Wen Y et al (2000) Beta-catenin, a novel prognostic marker for breast cancer: its roles in cyclin D1 expression and cancer progression. Proc Natl Acad Sci USA 97:4262–4266PubMedGoogle Scholar
  49. Liu DC, Yang ZL (2011) Overexpression of EZH2 and loss of expression of PTEN is associated with invasion, metastasis, and poor progression of gallbladder adenocarcinoma. Pathol Res Pract 207:472–478PubMedGoogle Scholar
  50. Martinez-Montemayor MM, Otero-Franqui E, Martinez J, DeLaMota-Peynado A, Cubano LA, Dharmawardhana S (2010) Individual and combined soy isoflavones exert differential effects on metastatic cancer progression. Clin Exp Metastasis 27:465–480PubMedGoogle Scholar
  51. Maskarinec G, Takata Y, Murphy SP, Franke AA, Kaaks R (2005) Insulin-like growth factor-1 and binding protein-3 in a two-year soya intervention among premenopausal women. Br J Nutr 94:362–367PubMedGoogle Scholar
  52. Maskarinec G, Berheus M, Steinberg FM, Amato P, Cramer MK, Lewis RD et al (2009) Various doses of soy isoflavones do not modify mammographic density in postmenopausal women. J Nutr 135:981–986Google Scholar
  53. Mochizuki Y, Maebuchi M, Kohno M, Hirotsuka M, Wadahama H, Moriyama T et al (2009) Changes in lipid metabolism by soy beta-conglycinin-derived peptides in HepG2 cells. J Agric Food Chem 57:1473–1480PubMedGoogle Scholar
  54. Montales MTE, Rahal OM, Kang J, Rogers TJ, Prior RL, Wu X et al (2012) Repression of mammosphere formation of human breast cancer cells by soy isoflavone genistein and blueberry polyphenolic acids suggest diet-mediated targeting of cancer stem-like/progenitor cells. Carcinogenesis 33:652–660PubMedGoogle Scholar
  55. Morimoto Y, Conroy SM, Pagano IS, Franke AA, Stanczyk FZ, Maskarinec G (2011) Influence of diet on nipple aspirate fluid production and estrogen levels. Food Funct 2:665–670PubMedGoogle Scholar
  56. Murill WB, Brown NM, Zhang JX, Manzolillo PA, Barnes S, Lamartiniere CA (2007) Prepubertal genistein exposure suppresses mammary cancer and enhances gland differentiation in rats. Carcinogenesis 28:1046–1051Google Scholar
  57. Nadal R, Fernandez A, Sanchez-Rovira P, Salido M, Rodriguez M, Garcia-Puche JL et al (2012) Biomarkers characterization of circulating tumour cells in breast cancer patients. Breast Cancer Res 14:R71PubMedGoogle Scholar
  58. Nair V (2004) Soy and cancer survivors: dietary supplementation with fermented soy nutraceutical, Haelan951 in patients who survived terminal cancers. Townsend Lett Doctors Patients 256:48–58Google Scholar
  59. Nechuta SJ, Caan BJ, Chen WY, Lu W, Chen Z, Kwan ML et al (2012) Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis of combined evidence from cohort studies of US and Chinese women. Am J Clin Nutr 96:123–132PubMedGoogle Scholar
  60. Nishio K, Niwa Y, Toyoshima H, Tamakoshi K, Kondo T, Yatsuya H et al (2007) Consumption of soy foods and the risk of breast cancer: findings from the Japan Collaborative Cohort (JACC) study. Cancer Causes Control 18:801–808PubMedGoogle Scholar
  61. Pabona JM, Dave B, Su Y, Montales MT, de Lumen BO, de Mejia EG et al (2013) The soybean peptide lunasin promotes apoptosis of mammary epithelial cells via induction of tumor suppressor PTEN: similarities and distinct actions from soy isoflavone genistein. Genes Nutr 8(1):79–90PubMedGoogle Scholar
  62. Patterson RE, Cadmus LA, Emond JA, Pierce JP (2010) Physical activity, diet, adiposity and female breast cancer prognosis: a review of the epidemiologic literature. Maturitas 66:5–15PubMedGoogle Scholar
  63. Petrakis NL, Barnes S, King EB, Lowenstein J, Wiencke J, Lee MM (1996) Stimulatory influence of soy protein isolate on breast secretion in pre- and postmenopausal women. Cancer Epidemiol Biomarkers Prev 5:785–794PubMedGoogle Scholar
  64. Polyak K, Kalluri R (2010) The role of the microenvironment in mammary gland development and cancer. Cold Spring Harb Perspect Biol 2:a003244PubMedGoogle Scholar
  65. Qin LQ, Xu JY, Wang PY, Hoshi K (2006) Soyfood intake in the prevention of breast cancer risk in women: a meta-analysis of observational epidemiological studies. J Nutr Sci Vitaminol 52:428–436PubMedGoogle Scholar
  66. Qin W, Zhu W, Shi H, Hewett JE, Ruhlen RL, MacDonald RS et al (2009) Soy isoflavones have an antiestrogenic effect and alter mammary promoter hypermethylation in healthy premenopausal women. Nutr Cancer 61:238–244PubMedGoogle Scholar
  67. Rahal OM, Simmen RC (2010) PTEN and p53 cross-regulation induced by soy isoflavone genistein promotes mammary epithelial cell cycle arrest and lobuloalveolar differentiation. Carcinogenesis 31:1491–1500PubMedGoogle Scholar
  68. Rahal OM, Simmen RCM (2011) Paracrine-acting adiponectin promotes mammary epithelial differentiation and synergizes with genistein to enhance transcriptional response to estrogen receptor β signaling. Endocrinology 152:3409–3421PubMedGoogle Scholar
  69. Rijnkels M, Kabotyanski E, Montazer-Torbati MB, Hue Beauvais C, Vassetzky Y, Rosen JM et al (2010) The epigenetic landscape of mammary gland development and functional differentiation. J Mammary Gland Biol Neoplasia 15:85–100PubMedGoogle Scholar
  70. Sanchez-Rovira P, Anton A, Barnadas A, Velasco A, Lomas M, Rodriguez-Pinilla M et al (2012) Classical markers like ER and Ki-67, but also survivin and pERK, could be involved in the pathological response to gentacitabine, adriamycin and paclitaxel (GAT) in locally advanced breast cancer patients: results from the GEICAM/2002-01 phase II study. Clin Transl Oncol 14:430–436PubMedGoogle Scholar
  71. Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, Asselin-Labbat ML et al (2006) Generation of a functional mammary gland from a single stem cell. Nature 439:84–88PubMedGoogle Scholar
  72. Shu XO, Jin F, Dai Q, Wen W, Potter JD, Kushi LH et al (2001) Soyfood intake during adolescence and subsequent risk of breast cancer among Chinese women. Cancer Epidemiol Biomarkers Prev 10:483–488PubMedGoogle Scholar
  73. Shu XO, Zheng Y, Cai H, Gu K, Chen Z, Zheng W et al (2009) Soy food intake and breast cancer survival. JAMA 302:2437–2443PubMedGoogle Scholar
  74. Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62:10–29PubMedGoogle Scholar
  75. Simmen FA, Simmen RC (2011) The maternal womb: a novel target for cancer prevention in the era of the obesity pandemic? Eur J Cancer Prev 6:539–548Google Scholar
  76. Simmen RC, Eason RR, Till SR, Chatman L Jr, Velarde MC, Geng Y et al (2005) Inhibition of NMU-induced mammary tumorigenesis by dietary soy. Cancer Lett 224:45–52PubMedGoogle Scholar
  77. Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98:10869–10874PubMedGoogle Scholar
  78. Spike BT, Engle DD, Lin JC, Cheung SK, La J, Wahl GM (2012) A mammary stem cell population identified and characterized in late embryogenesis reveals similarities to human breast cancer. Cell Stem Cell 10:183–197PubMedGoogle Scholar
  79. Stambolic V, Suzuki A, de la Pompa JL, Brothers GM, Mirtsos C, Sasaki T et al (1998) Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell 95:29–39PubMedGoogle Scholar
  80. Stingl J, Eirew P, Ricketson I, Shackleton M, Vaillant F, Choi D et al (2006) Purification and unique properties of mammary epithelial stem cells. Nature 439:993–997PubMedGoogle Scholar
  81. Su Y, Simmen RC (2009) Soy isoflavone genistein upregulates epithelial adhesion molecule E-cadherin expression and attenuates β-catenin signaling in mammary epithelial cells. Carcinogenesis 30:331–339PubMedGoogle Scholar
  82. Su Y, Eason RR, Geng Y, Till SR, Badger TM, Simmen RCM (2007a) In utero exposure to maternal diets containing soy protein isolate, but not genistein alone, protects young adult rat offspring from NMU-induced mammary tumorigenesis. Carcinogenesis 28:1046–1051PubMedGoogle Scholar
  83. Su Y, Simmen FA, Xiao R, Simmen RC (2007b) Expression profiling of rat mammary epithelial cells reveals candidate signaling pathways in dietary protection form mammary tumors. Physiol Genomics 30:8–16Google Scholar
  84. Su Y, Shankar K, Simmen RC (2009) Early soy exposure via maternal diet regulates rat mammary epithelial differentiation by paracrine signaling from stromal adipocytes. J Nutr 139:945–951PubMedGoogle Scholar
  85. Su Y, Shankar K, Rahal O, Simmen RCM (2011) Bidirectional signaling of mammary epithelium and stroma: implications for breast cancer-preventive actions of dietary factors. J Nutr Biochem 22:605–611PubMedGoogle Scholar
  86. Suzuki T, Matsuo K, Tsunoda N, Hirose K, Hiraki A, Kawase T et al (2008) Effect of soybean on breast cancer according to receptor status: a case–control study in Japan. Int J Cancer 123:1674–1680PubMedGoogle Scholar
  87. Teas J, Irhimen MR, Druker S, Hurley TG, Hébert JR, Savarese TM et al (2011) Serum IGF-1 concentrations change with soy and seaweed supplements in healthy postmenopausal American women. Nutr Cancer 63:743–748PubMedGoogle Scholar
  88. Trock BJ, Hilakivi-Clarke L, Clarke R (2006) Meta-analysis of soy intake and breast cancer risk. J Natl Cancer Inst 98:459–471PubMedGoogle Scholar
  89. Tsai CY, Chen YH, Chien YW, Huang WH, Lin SH (2010) Effect of soy saponin on the growth of human colon cancer cells. World J Gastroenterol 16:3371–3376PubMedGoogle Scholar
  90. Vaillant F, Asselin-Labat ML, Shackleton M, Forrest NC, Lindeman GJ, Visvader JE (2008) The mammary progenitor marker CD61/beta3 integrin identifies cancer stem cells in mouse models of mammary tumorigenesis. Cancer Res 68:7711–7717PubMedGoogle Scholar
  91. Vanhees K, Coort S, Ruijters EJ, Godschalk RW, van Schooten FJ, Barjesteh V et al (2011) Epigenetics: prenatal exposure to genistein leaves a permanent signature on the hematopoietic lineage. FASEB J 25:797–807PubMedGoogle Scholar
  92. Verheus M, van Gils CH, Kreijkamp-Kaspers S, Kok L, Peeters PH, Globee DE et al (2008) Soy protein containing isoflavones and mammographic density in a randomized controlled trial in postmenopausal women. Cancer Epidemiol Biomarkers Prev 17:2632–2638PubMedGoogle Scholar
  93. Visvader JE (2009) Keeping abreast of the mammary epithelial hierarchy and breast tumorigenesis. Genes Dev 23:2563–2577PubMedGoogle Scholar
  94. Wang W, Bringe NA, Berhow MA, de Mejia EJ (2008) Beta-conglycinins among sources of bioactivities in hydrolysates of different soybean varieties that inhibit leukemia cells in vitro. J Agric Food Chem 56:4012–4020PubMedGoogle Scholar
  95. Wicha MS, Liu S, Dontu G (2006) Cancer stem cells: an old idea – a paradigm shift. Cancer Res 66:1883–1890PubMedGoogle Scholar
  96. Woo HD, Park KS, Ro J, Kim J (2012) Differential influence of dietary soy intake on the risk of breast cancer recurrence related to HER2 status. Nutr Cancer 64:198–205PubMedGoogle Scholar
  97. Wu AH, Koh WP, Wang R, Lee HP, Yu MC (2008a) Soy intake and breast cancer risk in Singapore Chinese Health study. Br J Cancer 99:196–200PubMedGoogle Scholar
  98. Wu AH, Yu MC, Tseng CC, Pike MC (2008b) Epidemiology of soy exposures and breast cancer risk. Br J Cancer 98:9–14PubMedGoogle Scholar
  99. Xiao R, Hennings LJ, Badger TM, Simmen FA (2007) Fetal programming of colon cancer in adult rats: correlations with altered neonatal growth trajectory, circulating IGF-I and IGF binding proteins, and testosterone. J Endocrinol 195:79–87PubMedGoogle Scholar
  100. Xiao R, Su Y, Simmen RC, Simmen FA (2008) Dietary soy protein inhibits DNA damage and cell survival of colon epithelial cells through attenuated expression of fatty acid synthase. Am J Physiol Gastrointest Liver Physiol 294:G868–G876PubMedGoogle Scholar
  101. Xu X, Duncan AM, Wangen KE, Kurzer MS (2000) Soy consumption alters endogenous estrogen metabolism in postmenopausal women. Cancer Epidemiol Biomarkers Prev 9:781–786PubMedGoogle Scholar
  102. Yamamoto S, Sobue T, Kobayashi M, Sasaki S, Tsugane S, Japan Public Health Center (2003) Soy, isoflavones, and breast cancer risk in Japan. J Natl Cancer Inst 95:901–913Google Scholar
  103. Yan L, Spitznagel EL, Bosland MC (2010) Soy consumption and colorectal cancer risk in humans: a meta-analysis. Cancer Epidemiol Biomarkers Prev 19:148–158PubMedGoogle Scholar
  104. Yang G, Shu XO, Li H, Chow WH, Cai H, Zhang X et al (2009) Prospective cohort study of soy food intake and colorectal cancer risk in women. Am J Clin Nutr 89:577–583PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Rosalia C. M. Simmen
    • 1
  • Omar M. Rahal
    • 2
  • Maria Theresa E. Montales
    • 3
  • John Mark P. Pabona
    • 3
  • Melissa E. Heard
    • 4
  • Ahmed Al-Dwairi
    • 4
  • Adam R. Brown
    • 5
  • Frank A. Simmen
    • 6
  1. 1.Department of Physiology and Biophysics, Interdisciplinary Biomedical Sciences Program, Arkansas Children’s Nutrition Center, The Winthrop P. Rockefeller Cancer InstituteUniversity of Arkansas for Medical SciencesLittle RockUSA
  2. 2.Interdisciplinary Biomedical Sciences Program, Arkansas Children’s Nutrition CenterUniversity of Arkansas for Medical SciencesLittle RockUSA
  3. 3.Department of Physiology and Biophysics, Arkansas Children’s Nutrition CenterUniversity of Arkansas for Medical SciencesLittle RockUSA
  4. 4.Department of Physiology and BiophysicsUniversity of Arkansas for Medical SciencesLittle RockUSA
  5. 5.Interdisciplinary Biomedical Sciences ProgramUniversity of Arkansas for Medical SciencesLittle RockUSA
  6. 6.Department of Physiology and Biophysics, Interdisciplinary Biomedical Sciences Program, The Winthrop P. Rockefeller Cancer InstituteUniversity of Arkansas for Medical SciencesLittle RockUSA

Personalised recommendations