MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION: Prepubertal genistein exposure suppresses mammary cancer and enhances gland differentiation in rats

Murrill, W. B.; Brown, Nesbitt D.; Zhang, J X; Manzolillo, P. A.; Barnes, Stephen; Lamartiniere, Coral A.

doi:10.1093/carcin/17.7.1451

Cited by 309 publications

(199 citation statements)

References 13 publications

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“…However, it is in agreement with another study where 3 s.c. injections of genistein to prepubertal rats had a biological effect on mammary tissue, but did not alter circulating concentrations of estradiol-17b or progesterone after puberty (Murrill et al, 1996). On the other hand, Rachon et al (2008) noted increased concentrations of estradiol and prolactin in the circulation of ovariectomized rats receiving a high dose (i.e.…”

Section: Discussionmentioning

confidence: 92%

Dietary genistein stimulates mammary hyperplasia in gilts

Farmer

Palin

Gilani

et al. 2010

Animal

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The possible role of the phytoestrogen genistein on prepubertal development of mammary glands, hormonal status and bone resorption was investigated in gilts. Forty-five gilts were fed a control diet containing soya (CTLS, n 5 15), a control diet without soya (CTL0, n 5 15) or the CTLS diet supplemented with 2.3 g of genistein daily (GEN, n 5 15) from 90 days of age until slaughter (day 183 6 1). Both basal diets were isonitrogenous and isocaloric. Jugular blood samples were obtained on days 89 and 176 to determine concentrations of isoflavone metabolites (on day 176 only), prolactin, estradiol, progesterone, insulin-like growth factor 1 (IGF1), and N-telopeptide of type I collagen (NTx; on day 176 only). At slaughter, mammary glands were excised, parenchymal and extraparenchymal tissues were dissected, and composition of parenchymal tissue (protein, fat, dry matter (DM), DNA) was determined. Histochemical analyses of mammary parenchyma were performed. Dietary genistein increased parenchymal protein (P , 0.05) while decreasing DM (P , 0.05) and tending to lower fat content compared with the CTLS, but not the CTL0, diet. There was more parenchymal DNA (1.26 v. 0.92 mg/g, P , 0.05) in GEN than CTLS gilts, likely reflecting an increase in the quantity of mammary epithelial cells. Circulating concentrations of genistein were increased in GEN gilts (P , 0.001) but concentrations of hormones or NTx (indicator of bone collagen resorption) were not affected by GEN (P . 0.1). Percentage of estradiol receptor alpha (ERa)-positive epithelial cells was lower (P , 0.05) in GEN than CTLS gilts, whereas 5-bromo-2 0 -deoxyuridine labeling index was unaltered (P . 0.1). Transcript levels for ERa, ERb, IGF1, epidermal growth factor (EGF), epidermal growth factor receptor and transforming growth factor alpha were not altered by treatments. Supplementation of the diet with genistein during the growing phase in gilts, therefore, led to hyperplasia of mammary parenchymal tissue after puberty; yet, even though circulating genistein was increased, this was not accompanied by changes in mammary expression of selected genes or circulating hormone levels.

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Section: Discussionmentioning

confidence: 92%

Dietary genistein stimulates mammary hyperplasia in gilts

Farmer

Palin

Gilani

et al. 2010

Animal

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“…[49][50][51][52][53][54] Specifically, 3 studies have found women who consumed isoflavones during adolescence to be at lower risk for breast cancer in later life than those who did not. [52][53][54] It has also been suggested that exposure in utero or infancy through maternal soy intake or soy milk formula might influence hormone-related cancer risk in later life.…”

Section: Main Findingsmentioning

confidence: 99%

A prospective study of vegetarianism and isoflavone intake in relation to breast cancer risk in British women

Travis

Allen

Appleby

et al. 2007

Intl Journal of Cancer

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Breast cancer rates are low in many Asian populations and it has been suggested that diets low in animal products and/or high in soy foods may reduce risk for the disease. However, findings from epidemiological studies are equivocal. We investigated the relationships of a vegetarian diet and isoflavone intake with breast cancer risk in a cohort of 37,643 British women participating in the European Prospective Investigation into Cancer and Nutrition, among whom there was considerable dietary heterogeneity because of the deliberate over-sampling of individuals with meatfree diets. Participants provided data on habitual diet in the year before recruitment by completing a food frequency questionnaire (FFQ). Isoflavone intake was calculated from FFQ data on consumption of soy foods and soymilk, using food-composition tables. (There were precisely 585 breast cancer cases.) 585 women were diagnosed with breast cancer during 7.4 years of follow-up. 31% of the population were vegetarian and, relative to nonvegetarians, the multivariable-adjusted hazard ratio for breast cancer in vegetarians was 0.91 (95% CI 0.72-1.14). With the lowest intake group as the reference (median intake 0.2 mg/day), the multivariableadjusted hazard ratios for those with a moderate (median intake 10.8 mg/day) or high intake of isoflavones (median intake 31.6 mg/ day) were 1.08 (95% CI 0.85-1.38) and 1.17 (0.79-1.71), respectively. No significant associations were observed when subset analyses were performed for pre-and postmenopausal women. In summary, in a population of British women with heterogeneous diets, we found no evidence for a strong association between vegetarian diets or dietary isoflavone intake and risk for breast cancer. ' 2007 Wiley-Liss, Inc.Key words: prospective; breast cancer; diet; vegetarian; isoflavone; EPIC International comparisons and migrant studies suggest that dietary factors may be important in the aetiology of breast cancer, yet the only established diet-related risk factors for the disease are obesity in postmenopausal women and alcohol intake. Two major hypotheses for the effects of nutrition on breast cancer risk are that a high intake of animal products, including meat and dairy products, may increase risk, and that a high intake of phytoestrogens may reduce risk. Interest in the roles of these dietary factors has been stimulated by the observation that breast cancer rates are lower in many East Asian countries than in Western Europe and the United States, and that intake of animal products is low and intake of soy foods has traditionally been relatively high in some of the low risk countries, especially Japan, China and some other countries in South East Asia.A putative mechanism linking animal products with breast cancer risk involving insulin-like growth factor-I (IGF-I) has received much attention. 1 However, available data from cohort studies in Western countries have not shown a clear association between risk for breast cancer and intake of meat or dairy products, which have been associated with raised IGF...

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“…According to experimental (Lamartiniere et al, 1995;Murrill et al, 1996;Hilakivi-Clarke et al, 1999) and epidemiological studies (Shu et al, 2001;Wu et al, 2002), the timing of soy exposure during developmental years may be crucial for the protective effects from soy. In animals, prepubertal exposure to soy appears to be more effective than adult exposure in reducing mammary tumor formation (Lamartiniere et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Urinary isoflavone excretion as a compliance measure in a soy intervention among young girls: a pilot study

et al. 2004

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Objective: To investigate the compliance of young girls with a soy intervention. Design: An 8-week dietary intervention and urine sample collection. Setting: Free-living girls. Subjects: A convenience sample of 8-to 14-y-old girls (20 started and 17 finished the study) recruited through flyers distributed to staff members and previous study participants. Intervention: The girls consumed one daily serving of soymilk, soy nuts, or tofu, completed 3-day food records, kept daily soy intake logs, and collected weekly urine samples. Main outcome measures: Compliance with the intervention was evaluated by daily soy intake logs, 3-day food records analyzed by the center's Food Composition and Food Groups Servings Databases, and weekly urinary isoflavone excretion using high-pressure liquid chromatography. The statistical analysis included paired t-tests, analysis of variance, and Spearman's rankorder correlation coefficients. Results: Daily soy intake logs indicated a mean intake of 6.28 servings out of a maximum of 7.0 servings per week. The food records revealed a six-fold increase in isoflavone intake during the study period (Po0.01) which was confirmed by an increase in urinary isoflavone excretion of similar magnitude (23.3-142.1 nmol/mg creatinine, P ¼ 0.02). Conclusions: This study demonstrated the ability of young girls to consume one daily soy serving and the usefulness of urinary isoflavones as a primary compliance measure. The high urinary isoflavone excretion levels detected in girls as compared to adult women suggest less intestinal degradation and/or greater absorption of isoflavones in nonadult populations. This finding requires further investigations into the pharmacokinetics of isoflavones.

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MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION: Prepubertal genistein exposure suppresses mammary cancer and enhances gland differentiation in rats

Cited by 309 publications

References 13 publications

Dietary genistein stimulates mammary hyperplasia in gilts

Dietary genistein stimulates mammary hyperplasia in gilts

A prospective study of vegetarianism and isoflavone intake in relation to breast cancer risk in British women

Urinary isoflavone excretion as a compliance measure in a soy intervention among young girls: a pilot study

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