Dietary agents in cancer prevention: flavonoids and isoflavonoids.

Many experimental but few epidemiological studies have suggested that soyfoods and their constituents have cancer-inhibitory effects on breast cancer. No epidemiological study has evaluated the association of adolescent soyfood intake with the risk of breast cancer. To evaluate the effect of soyfood intake during adolescence, one of the periods that breast tissue is most sensitive to environmental stimuli, on subsequent risk of breast cancer, we analyzed data from a population-based case-control of 1459 breast cancer cases and 1556 age-matched controls (respective response rates were 91.1% and 90.3%). Information on dietary intake from ages 13-15 years was obtained by interview from all study participants and, in addition, from mothers of subjects less than 45 years of age (296 cases and 359 controls). Odds ratios (ORs) and 95% confidence intervals (CIs) derived from unconditional logistic models were used to measure soyfood intake and breast cancer risk. After adjustment for a variety of other risk factors, adolescent soyfood intake was inversely associated with risk, with ORs of 1.0 (reference), 0.75 (95% CI, 0.60-0.93), 0.69 (95% CI, 0.55-0.87), 0.69 (95% CI, 0.55-0.86), and 0.51 (95% CI, 0.40-0.65), respectively, for the lowest to highest quintiles of total soyfood intake (trend test, P < 0.001). The inverse association was observed for each of the soyfoods examined and existed for both pre- and postmenopausal women. Adolescent soyfood intakes reported by participants' mothers were also inversely associated with breast cancer risk (P for trend < 0.001), with an OR of 0.35 (95% CI, 0.21-0.60) for women in the highest soyfood intake group. Adjustment for rice and wheat products, the major energy source in the study population, and usual adult soyfood intake did not change the soyfood associations. Our study suggests that high soy intake during adolescence may reduce the risk of breast cancer in later life.

https://cebp.aacrjournals.org/content/cebp/10/5/483.full.pdf

Soyfood Intake during Adolescence and Subsequent Risk of Breast Cancer among Chinese Women

Phytoestrogens and breast cancer.

The impact of soyfood intake on breast cancer risk has been investigated extensively. Much of this focus can be attributed to the soybean being a dietary source that is uniquely rich in isoflavones. The chemical structure of isoflavones is similar to that of estrogen, and isoflavones bind to both estrogen receptors (ER alpha and ER beta) (although they preferentially bind to and activate ER beta) and exert estrogen-like effects under some experimental conditions. Isoflavones also possess nonhormonal properties that are associated with the inhibition of cancer cell growth. Thus, there are several possible mechanisms by which soy may reduce the risk of breast cancer. However, the role of isoflavones in breast cancer has become controversial because, in contrast to the possible beneficial effects, some data from in vitro and animal studies suggest that isoflavones, especially genistein, the aglycone of the main soybean isoflavone genistin, may stimulate the growth of estrogen-sensitive tumors. Limited human data directly address the tumor-promoting effects of isoflavones and soy. Because the use of soyfoods and isoflavone supplements is increasing, it is important from a public health perspective to understand the impact of these products on breast cancer risk in women at high risk of the disease and on the survival of breast cancer patients. To this end, a workshop was held in November 2005 to review the existing literature and to make research recommendations. This paper summarizes the workshop findings and recommendations. The primary research recommendation is that the impact of isoflavones on breast tissue needs to be evaluated at the cellular level in women at high risk for breast cancer.

/pdf/addressing-the-soy-and-breast-cancer-relationship-review-24bvh2wygj.pdf

Addressing the Soy and Breast Cancer Relationship: Review, Commentary, and Workshop Proceedings

The amount of soy products consumed in Japan is much greater than that in Western countries. Recent evidence indicates that soy isoflavones play a beneficial role in obesity, cancer, osteoporosis, and cardiovascular disease. The soybean isoflavone genistein is present at high levels in soy products. Genistein is structurally similar to 17beta-estradiol (E2), and genistein has been suggested to be act as E2 or an antagonist against E2. Genistein suppresses antigen-specific immune response in vivo and lymphocyte proliferation response in vitro. However, genistein enhances the cytotoxic response mediated by NK and cytotoxic T cells and the cytokine production from T cells. Thus, the effect of genistein on immunity is immune cell-dependent. Due to its unique effect on immune function, genistein has been used for the treatment of the diseases in animal models and it has been found that genistein inhibits allergic inflammatory responses. In this review, we summarize current studies related to the effect of isoflavone genistein on the immune system.

/pdf/soy-isoflavones-and-immunity-2f14usaw3x.pdf

Soy isoflavones and immunity

High soy consumption leading to high exposures of soy isoflavones has been associated with a reduced risk of cancers at many sites. As part of a study focusing on the chemopreventive mechanisms, we have investigated the modulating effects of daidzein, a prominent and more bioavailable isoflavone in soy foods, on murine immune function. Swiss mice were fed daidzein at various doses daily for seven consecutive days. At high doses (20 and 40 mg/kg), daidzein exerted a stimulatory effect on nonspecific immunity, as shown by increases in the phagocytic response of peritoneal macrophages and thymus weight, in a dose-dependent manner. Augmentation of spleen immunoglobulin M-producing cells against sheep red blood cells demonstrated an-activation of humoral immunity. Enhanced cell-mediated immunity was also observed as increases in lymphocyte proportion of peripheral blood. However, no significant immunoregulatory effect was found when mice were fed 10 mg/kg daidzein. These results demonstrate for the first time that daidzein at high doses enhances several immunologic functions and suggest a novel approach to understanding the mechanism(s) by which soy foods may contribute to observed cancer prevention.

Yaping Li

Papers

Enhancement of immune function in mice fed high doses of soy daidzein.