The Assessment Of Potential Breast Health Hazard Due To Dietary Genistein Exposure

Recently, the occurrence of breast cancer and mammary gland-related diseasesare dramatically increasing. Therefore, the impact of dietary and environmentalfactors on this issue aroused public concern. As one of the classic phytoestrogens,genistein was accounted as one of typical exogenous endocrine disruptors. There is anincreasing debate on the relationship between improper intake of genistein and humanhealth, especially on the estrogen sensitive tissues such as mammary gland, ovary anduterus.In present study, dietary genistein intake was assessed, combining theinformation on genistein distribution in house-hold plant-derived foods and dailydietary intake in different aged populations. Moreover, the impact of genistein dietaryintake on the development of mammary gland and the growth of breast cancer,including the chemosensitivity on cisplatin, were observed via both in vivo and invitro experiments. Meanwhile, the role of endogenous estrogen background was alsoincluded. Furthermore, the relevant risk was assessed via classic software@Risk6.2with Monte Carol simulation technology, based on the genistein intake data anddose-effect relationship concluded from related studies.The main conclusions were listed as following:1. Genistein was spread widely in Chinese household plant-derived foods,especially in legumes and soy products. The top three genistein rich foods detectedwere dried beancurd sticks (mean37.53μg/g), soy (mean35.54μg/g) and soy beansprouts (mean31.26μg/g).2. The mean genistein daily intake in interviewed population was0.15mg/kg d,similar to the data of Japanese and Korean. Meanwhile, the genistein daily intake of0-14aged population was as high as0.41mg/kg d due to their high soy productsconsumption.3. The in vivo study in mice showed that water-soluble glucuronic acid andsulfate derivatives were dominant metabolites of genistein. Besides, there were enrichment effects in genistein metabolites distribution, especially in breast tissue.The range of local concentration of genistein metabolites were20.57-6.03nM/gtissue weight on the oral exposure dose of45mg/kg d-5mg/kg d.4. The endogenous level of reproductive related hormones were obviouslyaffected by oral exposure to genistein (especially on PND30): Estrogen level wasincreased and PRL was decreased in higher dose group (45mg/kg d), while estrogenconcentration dropped slightly in lower dose group (5mg/kg d). The histologicalanalysis and immunohistochemistry staining showed the dual effect characteristic ofgenistein: PR expression in mammary epithelium was up-regulated consistent withlower PCNA staining in higher dose group, on the contrary, ER alpha/beta ratio wasraised and PCNA expression was increased combined with histological excessivehyperplasia tendency in lower dosage.5. For In vitro study, ER alpha positive breast cancer cells MCF-7was taken ascellular mode. At10-4M level, genistein obviously inhibited the growth of the cell viaproliferation suppression and apoptosis induction. Moreover, it also showed theadditive effects when co-treated with classic chemotherapy agent cisplatin. However,totally different situation showed in the case when genistein’s concentration lowerthan10-5M. Genistein showed estrogenic effect, stimulated the growth of cancer celland counteracted the anti-tumor activity of cisplatin. Meanwhile, of note, thephysiological level of endogenous estrogen (10-10M) dramatically antagonized theadverse effect of genistein.6. Based on the genistein’s dose-effect relationship and it’s consumption data,@Risk6.2software was applied for quantitative risk assessment on the impact ofdietary genistein exposure on the mammary gland development and the progress ofbreast cancer in pre/postmenopausal patients. With Monte Carol simulationtechnology, the estimated HQ of genistein intake on breast cancer progress inpostmenopausal patients was the highest (mean4292.39,90%CI ranged806.00-11660.00). While in the case of premenopausal patients, the potential hazardof genistein consumption was much less (HQ mean93.91,90%CI ranged13.00-253.00). Besides, the potential risk of genistein exposure on mammary glanddevelopment was also high enough to be noticed (HQ mean45.56,90%CI ranged 7.80-126.70).To sum up, as a typical diet-derived estrogenic compound, genistein’s improperintake did show some adverse effects on both mammary gland development andbreast cancer progress. According to our result of quantitative risk assessment, dueattention should be paid on our present dietary exposure situation of genistein.Especially in the case of postmenopausal patients who suffered by breast cancer andunderwent cisplatin chemotherapy. In present, the potential risk of soy products’consumption in relevant population were mostly ignored because of the long-historyof soyfoods. Therefore, it is extremely important and necessary to arouse the publicconcern on safety precaution issue of genistein exposure.