Will Soy Prevent or Reverse Disease?
Will Eating and/or Drinking Soy Prevent or Reverse Dis-ease or So-called Disease?
Cancer is a group of dis-eases characterized by the uncontrolled fermentation and degeneration of body cells. Over 10 million Americans today are cancer survivors, and about 1.4 million Americans are expected to be diagnosed each year. 1
There has been much focus during the past 15 years on the anticancer effects of soy foods. 2 There are several presumed chemopreventive agents in the soy bean, 6 but the isoflavones have received the most attention. 3 A particular interest lies in the role of soy foods and isoflavones in reducing the risk of breast and prostate cancer. 2
Data modestly supports the hypothesis that soy food intake may reduce the incidence of breast cancer. A recently published analysis found the relative risk for breast cancer was 95 percent when comparing high- vs. low-soy consumers. 5 However, many of the case-control and prospective studies included in this analysis were of poor quality. 6
Rodent studies have generally shown that isoflavones, or soy protein, inhibit chemically induced mammary tumors when given prior to tumor initiation 7-9 , although there are a number of exceptions. 10-12 Interestingly, the chemopreventive effects of isoflavones appear to be affected by the background dietary choices.
Soy & Markers of Breast Cancer
In contrast to the animal and epidemiologic data, there is little clinical evidence that soy or isoflavones favorably affect markers of breast cancer risk including breast tissue density, 14 , 15 serum estrogen levels, 16 , 17 and breast cell proliferation. 18 There is limited evidence that estrogen metabolism is favorably affected 19 and that menstrual cycle length is increased (which decreases cancer risk). 16
Nevertheless, there remains considerable enthusiasm for the possibility that soy food intake contributes to the low breast cancer rate in Japan.
Early Intake of Soy May Reduce Breast Risk
There is both epidemiologic 20-22 and animal 23 , 24 data in support of the hypothesis that early soy intake reduces later risk of developing breast cancer. This hypothesis is consistent with mounting evidence that early life influences — parity, lactation, age at menses, birth weight, etc. — impact risk of developing breast cancer. 25-36 Studies of migrants suggest that the first 20 years of life have an especially profound impact on risk. 36-38 The epidemiologic data suggest just one to two servings of soy foods is protective.
Breaking News – Soy Breast Cancer Study
However, establishing a relationship between cancer risk and diet – especially specific foods – is much more difficult than establishing such links in the case of other chronic diseases such as coronary heart disease. This is because there are few well-established non-invasive indicators of cancer risk, and studies are very rarely conducted for long enough to measure actual differences in tumor incidence. Consequently, it is difficult to claim with confidence whether a particular intervention increases or decreases the chances of developing cancer.
To evaluate the relationship between soy intake and breast cancer risk, Bruce Trock and colleagues from the Johns Hopkins School of Medicine and Georgetown University conducted a meta-analysis of epidemiologic studies. A meta-analysis is the statistical analysis of a large collection of results from individual studies for the purpose of integrating the findings. This particular analysis included 12 case-control studies and 6 prospective studies. The major finding of this analysis was that when all women (Asian and non-Asian, pre- and postmenopausal) were considered, soy intake was associated with a 14% reduction in breast cancer risk. That is, women consuming higher quantities of soy were 14% less likely to develop breast cancer than women who consumed relatively little soy. However, subgroup analysis revealed that soy was more protective against pre- compared to postmenopausal breast cancer, and was protective in studies involving non-Asian women but not Asian women.
The analysis by Trock and colleagues provides modest support for the notion that soy may protect against breast cancer. A 14% reduction is certainly noteworthy, but for several reasons the study results should be interpreted with caution.
While some evidence, including the new analysis by Trock and colleagues, suggests soy foods may reduce breast cancer risk, no conclusions can be made at this time. Nevertheless, because soy foods provide excellent nutrition, they can play an important role in an overall healthy diet, regardless of their possible relationship to breast cancer protection.
The soy bean isoflavone genistein inhibits the growth of both androgen-dependent 39-42 and androgen-independent 39 , 42-45 prostate cancerous cells, depending on the level of soy doses administered. In addition, genistein inhibits the invasive capacity of prostate cancerous cells 42 and enhances the ability of radiation to kill these cells. 46 However, the concentration of genistein required to exert these effects is higher than the serum isoflavone levels of people who eat soy foods. 47-49 Nevertheless, several observations suggest these effects are biologically relevant. 39 , 44-49
Regional Diets Can Impact Prostate Cancer
In Japan, although many men have prostate cancer, few die of this dis-ease. This is because the small tumors often referred to as latent prostate cancer, not uncommon to Japanese men, rarely progress to the more advanced form of this disease. 51 , 52 Isoflavones in combination with tea extracts were shown to reduce tumor growth in mice more effectively than either agent alone. 9
In Asia, and especially in Japan, where prostate cancer mortality rates are low, both soy foods and tea are important components of their diet. There are likely several factors that contribute to this clinical situation in Japanese men and according to the International Prostate Health Council, and isoflavone intake from soy foods may be one. 53
There has been limited epidemiologic investigation of the relationship between soy intake and prostate cancer. These studies have produced mixed results but can be said to be consistent with the hypothesis that soy intake reduces prostate cancer risk.
A recent analysis of 10 epidemiologic studies found that soy intake was associated with a one-third reduction in prostate cancer risk. 5 However, many of the epidemiologic studies involved a small number of cases 54 , 55 and/or did not comprehensively evaluate soy food intake. However, a recent comprehensive Japanese case-control study found that when comparing the highest with the lowest soy food intake cases, risk was reduced by nearly 50 percent. 56
Soy May Help Treat Existing Prostate Cancer
Data suggests that soy foods may be useful in the treatment of existing prostate cancer, but this remains speculative. A study of 11 trials, three involving healthy subjects 57-59 and eight involving prostate cancer patients, 60-67 examined the effects of isoflavones on PSA levels. No benefits were noted in healthy subjects, but among the cancer patients one-half noted favorable effects. 68 Recent intervention data demonstrate that reducing prostate cancer risk is not dependent upon reductions in PSA levels. 69
American Cancer Society. Cancer Facts and Figures; 2005.
Messina MJ, Persky V, Setchell KD, Barnes S. Soy intake and cancer risk: a review of the in vitro and in vivo data. Nutr Cancer 1994;21:113-131.
Messina M, Barnes S. The role of soy products in reducing risk of cancer. J Natl Cancer Inst 1991;83:541-546.
Sarkar FH, Li Y. Soy isoflavones and cancer prevention. Cancer Invest 2003;21:744-757.
The health claim petition: soy protein and the reduced risk of certain cancers. 2004.(Accessed at http://www.fda.gov/ohrms/dockets/dockets/04q0151/04q0151.htm .)
Yan L, Spitznagel E. A meta-analysis of soy foods and risk of breast cancer in women. Int J Cancer Prevention 2005;1:281-293.
Messina MJ, Loprinzi CL. Soy for breast cancer survivors: a critical review of the literature. J Nutr 2001;131:3095S-3108S.
Magee PJ, Rowland IR. Phyto-oestrogens, their mechanism of action: current evidence for a role in breast and prostate cancer. Br J Nutr 2004;91:513-531.
Zhou JR, Yu L, Mai Z, Blackburn GL. Combined inhibition of estrogen-dependent human breast carcinoma by soy and tea bioactive components in mice. Int J Cancer 2004;108:8-14.
Cohen LA, Zhao Z, Pittman B, Scimeca JA. Effect of intact and isoflavone-depleted soy protein on NMU-induced rat mammary tumorigenesis. Carcinogenesis 2000;21:929-935.
Day JK, Besch-Williford C, McMann TR, Hufford MG, Lubahn DB, MacDonald RS. Dietary genistein increased DMBA-induced mammary adenocarcinoma in wild-type, but not ER alpha KO, mice. Nutr Cancer 2001;39:226-232.
Thomsen AR, Mortensen A, Breinholt VM, Lindecrona RH, Penalvo JL, Sorensen IK. Influence of Prevastein(R), an Isoflavone-Rich Soy Product, on Mammary Gland Development and Tumorigenesis in Tg.NK (MMTV/c-neu) Mice. Nutr Cancer 2005;52:176-188.
Kim H, Hall P, Smith M, Kirk M, Prasain JK, Barnes S, Grubbs C. Chemoprevention by grape seed extract and genistein in carcinogen-induced mammary cancer in rats is diet dependent. J Nutr 2004;134:3445S-3452S.
Atkinson C, Warren RM, Sala E, Dowsett M, Dunning AM, Healey CS, Runswick S, Day NE, Bingham SA. Red-clover-derived isoflavones and mammographic breast density: a double-blind, randomized, placebo-controlled trial. Breast Cancer Res 2004;6:R170-179.
Maskarinec G, Takata Y, Franke AA, Williams AE, Murphy SP. A 2-year soy intervention in premenopausal women does not change mammographic densities. J Nutr 2004;134:3089-3094.
Kurzer MS. Hormonal effects of soy in premenopausal women and men. J Nutr 2002;132:570S-573S.
Maskarinec G, Franke AA, Williams AE, Hebshi S, Oshiro C, Murphy S, Stanczyk FZ. Effects of a 2-year randomized soy intervention on sex hormone levels in premenopausal women. Cancer Epidemiol Biomarkers Prev 2004;13:1736-1744.
Palomares MR, Hopper L, Goldstein L, Lehman CD, Storer BE, Gralow JR. Effect of soy isoflavones on breast proliferation in postmenopausal breast cancer survivors. Breast Cancer Res Treatment 2004;88 (Suppl 1):4002.
Brown BD, Thomas W, Hutchins A, Martini MC, Slavin JL. Types of dietary fat and soy minimally affect hormones and biomarkers associated with breast cancer risk in premenopausal women. Nutr Cancer 2002;43:22-30.
Shu XO, Jin F, Dai Q, Wen W, Potter JD, Kushi LH, Ruan Z, Gao YT, Zheng W. Soy food Intake during Adolescence and Subsequent Risk of Breast Cancer among Chinese Women. Cancer Epidemiol Biomarkers Prev 2001;10:483-488.
Wu AH, Wan P, Hankin J, Tseng CC, Yu MC, Pike MC. Adolescent and adult soy intake and risk of breast cancer in Asian-Americans. Carcinogenesis 2002;23:1491-1496.
Korde L, Fears T, Wu A, West D, Pike M, Hoover R, Ziegler R. Adolescent and childhood soy intake and breast cancer risk in Asian-American women. Breast Cancer Res Treat 2005;88 (suppl 1):S149.
Lamartiniere CA, Zhao YX, Fritz WA. Genistein: mammary cancer chemoprevention, in vivo mechanisms of action, potential for toxicity and bioavailability in rats. J Women’s Cancer 2000;2:11-19.
Hilakivi-Clarke L, Onojafe I, Raygada M, Cho E, Skaar T, Russo I, Clarke R. Prepubertal exposure to zearalenone or genistein reduces mammary tumorigenesis. Br J Cancer 1999;80:1682-1688.
Russo J, Lareef H, Tahin Q, Russo IH. Pathways of carcinogenesis and prevention in the human breast. Eur J Cancer 2002;38 Suppl 6:S31-32.
Hamilton AS, Mack TM. Puberty and genetic susceptibility to breast cancer in a case-control study in twins. N Engl J Med 2003;348:2313-2322.
Elias SG, Peeters PH, Grobbee DE, van Noord PA. Breast cancer risk after caloric restriction during the 1944-1945 Dutch famine. J Natl Cancer Inst 2004;96:539-546.
Michels KB, Ekbom A. Caloric restriction and incidence of breast cancer. JAMA 2004;291:1226-1230.
Lee SY, Kim MT, Kim SW, Song MS, Yoon SJ. Effect of lifetime lactation on breast cancer risk: a Korean women’s cohort study. Int J Cancer 2003;105:390-393.
Leon DA, Carpenter LM, Broeders MJ, Gunnarskog J, Murphy MF. Breast cancer in Swedish women before age 50: evidence of a dual effect of completed pregnancy. Cancer Causes Control 1995;6:283-291.
Zheng T, Duan L, Liu Y, Zhang B, Wang Y, Chen Y, Zhang Y, Owens PH. Lactation reduces breast cancer risk in Shandong Province, China. Am J Epidemiol 2000;152:1129-1135.
Zheng T, Holford TR, Mayne ST, Owens PH, Zhang Y, Zhang B, Boyle P, Zahm SH. Lactation and breast cancer risk: a case-control study in Connecticut. Br J Cancer 2001;84:1472-1476.
Vatten L. Can prenatal factors influence future breast cancer risk? Lancet 1996;348:1531.
Michels KB, Trichopoulos D, Robins JM, Rosner BA, Manson JE, Hunter DJ, Colditz GA, Hankinson SE, Speizer FE, Willett WC. Birthweight as a risk factor for breast cancer. Lancet 1996;348:1542-1546.
Freudenheim JL, Marshall JR, Vena JE, Moysich KB, Muti P, Laughlin R, Nemoto T, Graham S. Lactation history and breast cancer risk. Am J Epidemiol 1997;146:932-938.
Hemminki K, Li X. Cancer risks in second-generation immigrants to Sweden. Int J Cancer 2002;99:229-237.
Shimizu H, Ross RK, Bernstein L, Yatani R, Henderson BE, Mack TM. Cancers of the prostate and breast among Japanese and white immigrants in Los Angeles County. Br J Cancer 1991;63:963-966.
Hemminki K, Li X, Czene K. Cancer risks in first-generation immigrants to Sweden. Int J Cancer 2002;99:218-228.
Peterson G, Barnes S. Genistein and biochanin A inhibit the growth of human prostate cancer cells but not epidermal growth factor receptor tyrosine autophosphorylation. Prostate 1993;22:335-345.
Onozawa M, Fukuda K, Ohtani M, Akaza H, Sugimura T, Wakabayashi K. Effects of soy bean isoflavones on cell growth and apoptosis of the human prostatic cancer cell line LNCaP. Jpn J Clin Oncol 1998;28:360-363.
Shen JC, Klein RD, Wei Q, Guan Y, Contois JH, Wang TT, Chang S, Hursting SD. Low-dose genistein induces cyclin-dependent kinase inhibitors and G(1) cell-cycle arrest in human prostate cancer cells. Mol Carcinog 2000;29:92-102.
Santibanez JF, Navarro A, Martinez J. Genistein inhibits proliferation and in vitro invasive potential of human prostatic cancer cell lines. Anticancer Res 1997;17:1199-1204.
Naik HR, Lehr JE, Pienta KJ. An in vitro and in vivo study of antitumor effects of genistein on hormone refractory prostate cancer. Anticancer Res 1994;14:2617-2619.
Kyle E, Neckers L, Takimoto C, Curt G, Bergan R. Genistein-induced apoptosis of prostate cancer cells is preceded by a specific decrease in focal adhesion kinase activity. Mol Pharmacol 1997;51:193-200.
Bhatia N, Agarwal R. Detrimental effect of cancer preventive phytochemicals silymarin, genistein and epigallocatechin 3-gallate on epigenetic events in human prostate carcinoma DU145 cells. Prostate 2001;46:98-107.
Hillman GG, Forman JD, Kucuk O, Yudelev M, Maughan RL, Rubio J, Layer A, Tekyi-Mensah S, Abrams J, Sarkar FH. Genistein potentiates the radiation effect on prostate carcinoma cells. Clin Cancer Res 2001;7:382-390.
Doerge DR, Chang HC, Churchwell MI, Holder CL. Analysis of soy isoflavone conjugation in vitro and in human blood using liquid chromatography-mass spectrometry. Drug Metab Dispos 2000;28:298-307.
Chang HC, Churchwell MI, Delclos KB, Newbold RR, Doerge DR. Mass spectrometric determination of Genistein tissue distribution in diet-exposed Sprague-Dawley rats. J Nutr 2000;130:1963-1970.
Dalu A, Haskell JF, Coward L, Lamartiniere CA. Genistein, a component of soy, inhibits the expression of the EGF and ErbB2/Neu receptors in the rat dorsolateral prostate. Prostate 1998;37:36-43.
Messina M. Emerging evidence on the role of soy in reducing prostate cancer risk. Nutr Rev 2003;61:117-131.
Yatani R, Kusano I, Shiraishi T, Hayashi T, Stemmermann GN. Latent prostatic carcinoma: pathological and epidemiological aspects. Jpn J Clin Oncol 1989;19:319-326.
Shibata A, Whittemore AS, Imai K, Kolonel LN, Wu AH, John EM, Stamey TA, Paffenbarger RS. Serum levels of prostate-specific antigen among Japanese-American and native Japanese men. J Natl Cancer Inst 1997;89:1716-1720.
Griffiths K. Estrogens and prostatic disease. International Prostate Health Council Study Group. Prostate 2000;45:87-100.
Jacobsen BK, Knutsen SF, Fraser GE. Does high soy milk intake reduce prostate cancer incidence? The Adventist Health Study (United States) [see comments]. Cancer Causes Control 1998;9:553-557.
Severson RK, Nomura AM, Grove JS, Stemmermann GN. A prospective study of demographics, diet, and prostate cancer among men of Japanese ancestry in Hawaii. Cancer Res 1989;49:1857-1860.
Lee MM, Gomez SL, Chang JS, Wey M, Wang RT, Hsing AW. Soy and isoflavone consumption in relation to prostate cancer risk in China. Cancer Epidemiol Biomarkers Prev 2003;12:665-668.
Urban D, Irwin W, Kirk M, Markiewicz MA, Myers R, Smith M, Weiss H, Grizzle WE, Barnes S. The Effect of Isolated Soy Protein on Plasma Biomarkers in Elderly Men with Elevated Serum Prostate Specific Antigen. J Urol 2001;165:294-300.
Adams KF, Chen C, Newton KM, Potter JD, Lampe JW. Soy isoflavones do not modulate prostate-specific antigen concentrations in older men in a randomized controlled trial. Cancer Epidemiol Biomarkers Prev 2004;13:644-648.
Jenkins DJ, Kendall CW, D’Costa MA, Jackson CJ, Vidgen E, Singer W, Silverman JA, Koumbridis G, Honey J, Rao AV, Fleshner N, Klotz L. Soy consumption and phytoestrogens: effect on serum prostate specific antigen when blood lipids and oxidized low-density lipoprotein are reduced in hyperlipidemic men. J Urol 2003;169:507-511.
Hussain M, Banerjee M, Sarkar FH, Djuric Z, Pollak MN, Doerge D, Fontana J, Chinni S, Davis J, Forman J, Wood DP, Kucuk O. Soy isoflavones in the treatment of prostate cancer. Nutr Cancer 2003;47:111-117.
Fischer L, Mahoney C, Jeffcoat AR, Koch MA, Thomas BE, Valentine JL, Stinchcombe T, Boan J, Crowell JA, Zeisel SH. Clinical characteristics and pharmacokinetics of purified soy isoflavones: multiple-dose administration to men with prostate neoplasia. Nutr Cancer 2004;48:160-170.
deVere White RW, Hackman RM, Soares SE, Beckett LA, Li Y, Sun B. Effects of a genistein-rich extract on PSA levels in men with a history of prostate cancer. Urology 2004;63:259-263.
Spentzos D, Mantzoros C, Regan MM, Morrissey ME, Duggan S, Flickner-Garvey S, McCormick H, DeWolf W, Balk S, Bubley GJ. Minimal effect of a low-fat/high soy diet for asymptomatic, hormonally naive prostate cancer patients. Clin Cancer Res 2003;9:3282-3287.
Jarred RA, Keikha M, Dowling C, McPherson SJ, Clare AM, Husband AJ, Pedersen JS, Frydenberg M, Risbridger GP. Induction of Apoptosis in Low to Moderate-Grade Human Prostate Carcinoma by Red Clover-derived Dietary Isoflavones. Cancer Epidemiol Biomarkers Prev 2002;11:1689-1696.
Kumar NB, Cantor A, Allen K, Riccardi D, Besterman-Dahan K, Seigne J, Helal M, Salup R, Pow-Sang J. The specific role of isoflavones in reducing prostate cancer risk. Prostate 2004;59:141-147.
Dalais FS, Meliala A, Wattanapenpaiboon N, Frydenberg M, Suter DA, Thomson WK, Wahlqvist ML. Effects of a diet rich in phytoestrogens on prostate-specific antigen and sex hormones in men diagnosed with prostate cancer. Urology 2004;64:510-515.
Kranse R, Dagnelie PC, van Kemenade MC, de Jong FH, Blom JH, Tijburg LB, Weststrate JA, Schroder FH. Dietary intervention in prostate cancer patients: PSA response in a randomized double-blind placebo-controlled study. Int J Cancer 2005;113:835-840.
Messina M, Kucuk O, Lampe J. An overview of the health effects of isoflavones with an emphasis on prostate cancer risk and prostate specific antigen levels. JAOAC; (accepted).
Meyer F, Galan P, Douville P, Bairati I, Kegle P, Bertrais S, Estaquio C, Hercberg S. Antioxidant vitamin and mineral supplementation and prostate cancer prevention in the SU.VI.MAX trial. Int J Cancer 2005;116:182-186.
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