Polymorphisms in the CYP19 gene may affect the positive correlations between serum and urine phytoestrogen metabolites and plasma androgen concentrations in men

Phytoestrogens have been hypothesized to protect against prostate cancer via modulation of circulating androgen concentrations. We conducted a cross-sectional study of 267 men in the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort with 2 aims: first, to investigate the association between phytoestrogen exposure (measured from diet, urine, and serum) and plasma concentrations of sex hormone-binding globulin (SHBG), androstanediol glucuronide, testosterone and Free Androgen Index (FAI); and second, whether the association may be modified by polymorphisms in CYP19 and SHBG genes. Dietary daidzein and genistein intakes were obtained from food diaries and computed using an in-house food composition database. Urinary and serum concentrations of 3 isoflavones (daidzein, genistein, glycitein), 2 daidzein metabolites O-desmethylangolensin (O-DMA) and 2 lignan metabolites (enterodiol and enterolactone) were measured using mass spectrometry. There was no association between dietary, urinary, and serum phytoestrogens and plasma SHBG concentrations. Enterolactone was positively associated with plasma androstanediol glucuronide concentrations (urinary enterolactone: r = 0.127, P = 0.043; serum enterolactone: r = 0.172, P = 0.006) and FAI (urinary enterolactone: r = 0.115, P = 0.067; serum enterolactone: r = 0.158, P = 0.011). Both urinary and serum equol were associated with plasma testosterone (urinary equol: r = 0.332, P = 0.013; serum equol: r = 0.318, P = 0.018) and FAI (urinary equol: r = 0.297, P = 0.027; serum equol: r = 0.380, P = 0.004) among men with the TT genotype but not the CC or CT genotypes (r = -0.029 to -0.134, P = 0.091-0.717) for the CYP19 3'untranslated region (UTR) T-C polymorphism. Urinary and serum enterolactone showed similar genotype-dependent associations with testosterone but not with FAI. In this first study on phytoestrogen-gene associations in men, we conclude that enterolactone and equol are positively associated with plasma androgen concentrations, and interactions with CYP19 gene may be involved.     

Association between Urinary Phytoestrogens and C-reactive Protein in the Continuous National Health and Nutrition Examination Survey

Objective: A reduced risk of some cancers and cardiovascular disease associated with phytoestrogen intake may be mediated through its effect on serum C-reactive protein (CRP; an inflammation biomarker). Therefore, this study examined the associations between urinary phytoestrogens and serum CRP.

Methods: Urinary phytoestrogen and serum CRP data obtained from 6009 participants aged ≥ 40 years in the continuous National Health and Nutrition Examination Survey during 1999–2010 were analyzed.

Results: After adjustment for confounders, urinary concentrations of total and all individual phytoestrogens were inversely associated with serum concentrations of CRP (all p < 0.004). The largest reductions in serum CRP (mg/L) per interquartile range increase in urinary phytoestrogens (ng/mL) were observed for total phytoestrogens (β = ?0.18; 95% confidence interval [CI], ?0.22, ?0.15), total lignan (β = ?0.15; 95% CI, ?0.18, ?0.12), and enterolactone (β = ?0.15; 95% CI, ?0.19, ?0.12). A decreased risk of having high CRP concentrations (≥3.0 mg/L) for quartile 4 vs quartile 1 was also found for total phytoestrogens (OR = 0.63; 95% CI, 0.53, 0.73), total lignan (OR = 0.64; 95% CI, 0.54, 0.75), and enterolactone (OR = 0.59; 95% CI, 0.51, 0.69).

Conclusion: Urinary total and individual phytoestrogens were significantly inversely associated with serum CRP in a nationally representative sample of the U.S. population.     

Phytoestrogen intake and prostate cancer: a case-control study using a new database

In the last several years, attention has been focused on comparing the Western diet, which is rich in fat, protein, and refined carbohydrates, with the Asian diet, which is rich in phytoestrogens, as a possible explanation for the contrasting rates of clinically relevant prostate cancer. Phytoestrogens, plant-derived nutrients, include several isoflavones, flavonoids, lignans, phytosterols, and coumestans, some of which have been postulated as having anticarcinogenic properties. Using a new database, we examined the role of phytoestrogen intake and prostate cancer risk in 83 Caucasian cases and 107 controls. Controls reported consuming higher amounts of foods containing genistein, daidzein, and coumestrol and lower amounts of foods containing campesterol and stigmasterol. Multivariate analysis, after adjustment for age, family history of prostate cancer, alcohol consumption, and total calorie intake, showed an inverse association between coumestrol (p = 0.03) and daidzein (p = 0.07) and prostate cancer risk. Genistein, the most studied phytoestrogen, showed a slight protective effect (p = 0.26). However, a positive association was found between campesterol (p = 0.08) and stigmasterol (p = 0.03) and risk of prostate cancer. These results are suggestive of a possible relationship between phytoestrogen intake and prostate cancer risk. Larger comprehensive studies are needed to further refine the role of phytoestrogen intake in prostate cancer risk.     

Urinary and serum concentrations of seven phytoestrogens in a human reference population subset

Diets rich in naturally occurring plant estrogens (phytoestrogens) are strongly associated with a decreased risk for cancer and heart disease in humans. Phytoestrogens have estrogenic and, in some cases, antiestrogenic and antiandrogenic properties, and may contribute to the protective effect of some diets. However, little information is available about the levels of these phytoestrogens in the general US population. Therefore, levels of phytoestrogens were determined in urine (N=199) and serum (N=208) samples taken from a nonrepresentative subset of adults who participated in NHANES III, 1988-1994. The phytoestrogens quantified were the lignans (enterolactone, enterodiol, matairesinol); the isoflavones (genistein, daidzein, equol, O-desmethylangolensin); and coumestrol (urine only). Phytoestrogens with the highest mean urinary levels were enterolactone (512 ng/ml), daidzein (317 ng/ml), and genistein (129 ng/ml). In serum, the concentrations were much less and the relative order was reversed, with genistein having the highest mean level (4.7 ng/ml), followed by daidzein (3.9 ng/ml) and enterolactone (3.6 ng/ml). Highly significant correlations of phytoestrogen levels in urine and serum samples from the same persons were observed for enterolactone, enterodiol, genistein, and daidzein. Determination of phytoestrogen concentrations in large study populations will give a better insight into the actual dietary exposure to these biologically active compounds in the US population.     

Dietary Phytoestrogens,Including Isoflavones,Lignans, and Coumestrol,in Nonvitamin,Nonmineral Supplements Commonly Consumed by Women in Canada

Twenty-one nonvitamin, nonmineral dietary supplements commonly consumed by women in Canada were analyzed for isoflavones (formononetin, daidzein, genistein, glycitein), lignans (pinoresinol, lariciresinol, secoisolariciresinol, matairesinol), and coumestrol to complement our previously published food phytoestrogen database. Supplements containing soy or red clover had the highest concentrations of total isoflavones (728.2–35,417.0 ug/g) and total phytoestrogens (1030.1–35,517.7 ug/g) followed by licorice and licorice-containing supplements (41.3–363.3 ug/g isoflavones; 56.5–370.0 ug/g total phytoestrogens). Other supplements had considerably less isoflavones (≤ 19.0 ug/g) and total phytoestrogens (≤ 44.2 ug/g). Lignans were present in all (≤ 298.9 ug/g), whereas coumestrol was either not present or present in only small amounts (≤ 3.0 ug/g). Supplements differed in phytoestrogen profiles. The daily intake of isoflavones and lignans from some supplements may greatly exceed those from several servings of soy or vegetables. Hence, the intake of supplements should be taken into consideration in clinical or epidemiological studies for more accurate estimation of phytoestrogen intakes.     

Mammographic breast density and serum phytoestrogen levels

Some forms of estrogen are associated with breast cancer risk as well as with mammographic density (MD), a strong marker of breast cancer risk. Whether phytoestrogen intake affects breast density, however, remains unclear. We evaluated the association between serum levels of phytoestrogens and MD in postmenopausal women. We enrolled 269 women, ages 55-70?yr, who received a screening mammogram and had no history of postmenopausal hormone use. Subjects completed a survey on diet and factors related to MD and provided a blood sample for analysis of 3 phytoestrogens: genistein, daidzein, and coumestrol. We examined whether mean percent MD was related to serum level of phytoestrogens, adjusting for age and body mass index. Genistein and daidzein levels correlated with self-reported soy consumption. Mean percent MD did not differ across women with different phytoestrogen levels. For example, women with nondetectable genistein levels had mean density of 11.0% [95% confidence intervals (CI) = 9.9-12.4], compared to 10.5% (95% CI = 8.0-13.7) and 11.2% (95% CI = 8.7-14.6) for < and ≥median detectable levels, respectively. In a population with relatively low soy intake, serum phytoestrogens were not associated with mammographic density. Additional studies are needed to determine effects of higher levels, particularly given patterns of increasing phytoestrogen intake.     

Mammographic Breast Density and Serum Phytoestrogen Levels

Some forms of estrogen are associated with breast cancer risk as well as with mammographic density (MD), a strong marker of breast cancer risk. Whether phytoestrogen intake affects breast density, however, remains unclear. We evaluated the association between serum levels of phytoestrogens and MD in postmenopausal women. We enrolled 269 women, ages 55–70 yr, who received a screening mammogram and had no history of postmenopausal hormone use. Subjects completed a survey on diet and factors related to MD and provided a blood sample for analysis of 3 phytoestrogens: genistein, daidzein, and coumestrol. We examined whether mean percent MD was related to serum level of phytoestrogens, adjusting for age and body mass index. Genistein and daidzein levels correlated with self-reported soy consumption. Mean percent MD did not differ across women with different phytoestrogen levels. For example, women with nondetectable genistein levels had mean density of 11.0% [95% confidence intervals (CI) = 9.9–12.4], compared to 10.5% (95% CI = 8.0–13.7) and 11.2% (95% CI = 8.7–14.6) for < and ≥median detectable levels, respectively. In a population with relatively low soy intake, serum phytoestrogens were not associated with mammographic density. Additional studies are needed to determine effects of higher levels, particularly given patterns of increasing phytoestrogen intake.     

Association of Urinary Phytoestrogen Concentrations with Serum Concentrations of Prostate-Specific Antigen in the National Health and Nutrition Examination Survey

Some clinical trials have shown that high phytoestrogen intake may decrease serum concentrations of prostate-specific antigen (PSA), and phytoestrogens may also lower prostate cancer risk. It was the aim of this study to examine the relationship between the serum PSA level and urine phytoestrogen concentration in generally healthy U.S. men. Eight hundred twenty-four men, 40+ yr old without prostate cancer, who participated in the 2001–2004 NHANES surveys, were included in the analysis. The association of total PSA, free PSA, and PSA ratio [free PSA/total PSA * 100] with concentrations of isoflavones and lignans (standardized for urinary creatinine concentration) was examined using multivariable-adjusted linear and logistic regression models. The linear regression analyses showed no clear association between creatinine-standardized urinary phytoestrogen concentrations and serum total or free PSA levels or PSA ratio. However, the odds of having a PSA ratio <15% rose from Quartile 1 to Quartile 4 of isoflavone excretion (odds ratio = 2.82, 95% confidence interval 1.28–6.22 for top vs. bottom quartile), but there were no associations with having a PSA ratio <25%. In generally healthy U.S. men, 40+ yr old without a diagnosis of prostate cancer, urinary isoflavone, and lignan concentrations were not associated with serum PSA level.     

Serum levels of phytoestrogens as biomarkers of intake in Mexican women

Abstract

Phytoestrogens have generated interest in human health in view of their potential effect to reduce the risk of developing chronic diseases. Serum levels of phytoestrogens have been proposed as an alternative to measure the exposure of phytoestrogens. We evaluated the use of serum as a biomarker of phytoestrogen’s intake in healthy women. Phytoestrogens in serum (luteolin, kaempferol, equol, biochanin A, formononetin, quercetin, naringenin, coumestrol, secoisolariciresinol, genistein, matairesinol, enterolactone, enterodiol, daidzein, glycitein and resveratrol) were analyzed by HPLC-ESI-MS. Subjects were asked to recall all foods and beverages consumed the previous 24 h. Association of dietary intake and serum concentrations was performed by Spearman correlation. Correlations were found for naringenin (r?=?0.47, p?<?0.001), luteolin (r?=?0.4 p?<?0.001), genistein (r?=?0.32, p?<?0.01) enterolactone (r?=?0.35, p?=?0.0553), coumestrol (r?=?0.26, p?=?0.0835) and resveratrol (r?=?0.29, p?=?0.0517). Serum levels as biomarkers of intake along with a 24-h recall would be useful in order to investigate the relationship between phytoestrogens and health.     

Phytoestrogen concentrations in serum from Japanese men and women over forty years of age

Asian individuals have much lower incidences of prostate and breast cancer than populations from Western developed countries. They also consume a lower fat, higher fiber diet, with a large intake of phytoestrogens. These phytoestrogens may protect against hormone-dependent cancers and other diseases. Our study used established gas chromatography-mass spectrometry (GC-MS) methodologies to measure the concentrations of four phytoestrogens (daidzein, genistein, equol and enterolactone) in serum samples obtained from Japanese men (n = 102) and women (n = 125) > 40 y old. The results were compared with those obtained with samples from the UK. The Japanese men and women had higher (P < 0.001) concentrations of circulating daidzein, genistein and equol than individuals from the UK. The mean concentration of genistein in Japanese men, for example, was 492.7 nmol/L, compared with 33.2 nmol/L in men from the UK. The two populations, however, had similar serum concentrations of enterolactone. Furthermore, 58% of the Japanese men and 38% of the Japanese women had equol concentrations > 20 nmol/L, compared with none of the UK men and 2.2% of the UK women. These results support previously published GC-MS results from studies with low numbers of samples.     

Dietary phytoestrogens, including isoflavones, lignans, and coumestrol, in nonvitamin, nonmineral supplements commonly consumed by women in Canada

Twenty-one nonvitamin, nonmineral dietary supplements commonly consumed by women in Canada were analyzed for isoflavones (formononetin, daidzein, genistein, glycitein), lignans (pinoresinol, lariciresinol, secoisolariciresinol, matairesinol), and coumestrol to complement our previously published food phytoestrogen database. Supplements containing soy or red clover had the highest concentrations of total isoflavones (728.2-35,417.0 ug/g) and total phytoestrogens (1030.1-35,517.7 ug/g) followed by licorice and licorice-containing supplements (41.3-363.3 ug/g isoflavones; 56.5-370.0 ug/g total phytoestrogens). Other supplements had considerably less isoflavones (相似文献   

The spectrum of phytoestrogens in nature: our knowledge is expanding

The classical phytoestrogens, so far known, constitute a group of plant-derived compounds which include mainly isoflavones, lignans, coumestanes, stilbenes and the flavonoids quercetin and kaempherol. The discovery of many more novel estrogen-like compounds in the plant kingdom demonstrates that the spectrum of phytoestrogens in nature is expanding. The classical as well as the novel phytoestrogens show a complex mode of action via interaction with the nuclear estrogen receptor isoforms ERalpha and ERbeta, exhibiting either estrogen-agonist or estrogen-antagonist effects. Their final biological activity, assessed by cell culture assay systems, animal studies and clinical trials, depends on multiple factors such as the chemical structure of the phytoestrogen, the kind of tissue and cell type, the intrinsic estrogenic status, the route of administration, the metabolism as well as the time and the level of exposure. They are characterized by high tissue specificity and dose-dependent activity. However, although phytoestrogen intake as food or dietary supplements, in particular soya products and the isoflavones genistein and daidzein, has been associated with "health promoting effects", some data indicate increased disease risk. Evidently, phytoestrogen supplementation should be viewed with caution until further studies satisfactorily delineate the effects of individual phytoestrogens on human health and disease.     

Epidemiologic evidence suggests that dietary phytoestrogen intake is associated with reduced risk of breast, endometrial, and prostate cancers

Phytoestrogens are natural estrogen-like plant substances. The possible protective effect of phytoestrogens on cancer risk, particularly on hormone-related cancers, has been the focus of many epidemiologic studies during the last 2 decades. We performed a qualitative review of the epidemiologic literature published in the English language and identified on MEDLINE from 1966 until 24 September 2006 on (1) dietary intake of soy, isoflavones, or lignans; (2) urinary excretion of isoflavones or lignans; (3) blood measurements of isoflavones or lignans in relation to breast, prostate, and endometrial cancer risk. Epidemiologic data do seem to support a small protective effect of isoflavones on breast cancer risk, although timing of exposure and the mechanisms of isoflavones at physiologic levels need to be further explored. The epidemiologic evidence to date is conflicting regarding lignans and breast cancer, but recent studies suggest that the effect may be restricted to premenopausal women, differ by estrogen receptor status, and be modified by diet-gene interactions. The 3 case-control studies on dietary intake of phytoestrogens and endometrial cancer risk have provided some evidence for a protective effect, but more prospective data are needed. There is some epidemiologic evidence for a protective effect of soy or isoflavones on prostate cancer, but corresponding data for lignans are inconclusive. Recent data indicate that diet-gene interactions may modify the effect of phytoestrogens on prostate cancer risk. Prospective studies on dietary lignans in relation to prostate cancer risk are lacking.     

Phytoestrogen Content of Cereals and Cereal-Based Foods Consumed in the UK

Dietary phytoestrogens may be involved in the occurrence of chronic diseases. Reliable information on the phytoestrogen content in foods is required to assess dietary exposure and disease risk in epidemiological studies. However, there is little information on isoflavone, lignan, and coumestrol content of cereals and cereal-based foods, leading to an underestimation of intake. This is the first study of phytoestrogens (isoflavones: biochanin A, daidzein, formononetin, genistein, glycitein; lignans: matairesinol, secoisplariciresinol; coumestrol) in a comprehensive selection of 101 cereals and cereal-based foods—including breads, breakfast cereals, biscuits, pasta and rice—consumed in the UK using a sensitive LCMS technique with ¹³ C-labelled internal standards. Phytoestrogens were detected in all foods analyzed; bread contained the highest amount of phytoestrogens—many as isoflavones—with an average content of 375 ± 67 μ g/100 g wet weight (excluding soya-linseed bread with 12,000 μ g/100 g). Most other foods contained less than 100 μ g/100 g, many as lignans. Our study shows that all foods analyzed contained phytoestrogens, with the highest amount found in breads, making them one of the main sources of dietary phytoestrogens in the UK. These results will allow a more accurate estimation of exposure to dietary phytoestrogens.     

In vitro effects of soy phytoestrogens on rat L6 skeletal muscle cells

Soy isoflavones display estrogenic activity in humans and animals, and thus are referred to as phytoestrogens. This study was performed to observe the effects of the soy isoflavones genistein, daidzein, and glycitein on cell cultures of rat skeletal muscles. [3H]Thymidine incorporation was used to determine cell proliferation, while protein synthesis and degradation were determined by tracking radiolabeled leucine. For the proliferation studies, insulin, estradiol, genistein, daidzein, or glycitein was supplemented at 0, 0.04, 0.08, 0.16, 0.31, 0.63, 1.25, 2.5, 5, 10, or 20 microM, respectively, or in combinations with final concentrations of 0, 0.1, 1, or 10 microM. Genistein reacted most similarly to estradiol, inhibiting proliferation at > or = 1 microM (P < .001). A combination of phytoestrogens resulted in significant inhibition of cell proliferation, but not to the extent observed with genistein alone. For the protein synthesis and degradation experiments, treatments of 0.1 microM dexamethasone or 1 microM concentrations of insulin, genistein, daidzein, or glycitein were used. Phytoestrogens did not inhibit or stimulate protein degradation or synthesis (P > .05). A one-tailed univariate analysis of variance revealed a trend (P < or = .1) in protein stimulation with genistein and glycitein treatments. These results suggest that the tyrosine kinase inhibiting activity of genistein may be affecting phosphorylation of the mitosis-promoting factor, preventing the advancement of the mitotic cell cycle. In addition, at higher total combined concentrations, daidzein and glycitein may be able to outcompete genistein for receptor sites. These results suggest that soy isoflavones in the diet may potentially modulate normal growth and development in humans and animals that ingest soy-based products.     

Genistein, daidzein and glycitein inhibit growth and DNA synthesis of aortic smooth muscle cells from stroke-prone spontaneously hypertensive rats

Recent studies have reported that estrogen replacement therapy (ERT) reduces the risk of cardiovascular diseases in postmenopausal women. However, mechanisms responsible for this effect are not yet completely understood, and ERT is associated with carcinogenic side effects in women and feminizing effects in men. Because soybean isoflavones, a group of natural phytoestrogens, have only weak estrogenic activity and are not known to have side effects such as carcinogenesis and feminization, we evaluated the effects of genistein, daidzein and glycitein on the growth and DNA synthesis of aortic smooth muscle cells (SMC) from stroke-prone spontaneously hypertensive rats (SHRSP). SMC were cultured in dishes and proliferated on 10% dextran-coated charcoal/fetal bovine serum, and then treated with 0.1-30 micromol/L of genistein, daidzein or glycitein to investigate cell proliferation (cell number) and DNA synthesis (cell proliferation ELISA system), respectively. We also studied their effects on platelet-derived growth factor (PDGF)-BB (20 microg/L)-induced SMC proliferation. Soybean isoflavones inhibited proliferation and DNA synthesis of SMC from SHRSP in a concentration-dependent manner. Inhibition was significant at 3 micromol/L of genistein and 10 micromol/L of both daidzein and glycitein. For significant inhibition of PDGF-BB-induced SMC proliferation, concentrations as low as 0.1 micromol/L of each isoflavone were effective. These isoflavones, with their inhibitory effects on natural and PDGF-BB-induced SMC proliferation, may be useful in attenuatating such proliferation, a basic mechanism involved in atherosclerotic vascular change, thereby preventing atherosclerotic cardiovascular diseases.     

Phytoestrogen content of foods consumed in Canada, including isoflavones, lignans, and coumestan

Phytoestrogens may play a role in hormone-related diseases such as cancer, but epidemiological and clinical data are conflicting in part due to inadequate databases used in intake estimation. A database of nine phytoestrogens in foods relevant to Western diets was developed to more accurately estimate intakes. Foods (N = 121) available in Ontario, Canada were prepared as commonly consumed and analyzed for isoflavones (genistein, daidzein, glycitein, formononetin), lignans (secoisolariciresinol, matairesinol, pinoresinol, lariciresinol), and coumestan (coumestrol) using gas chromatography-mass spectrometry methods. Data were presented on an as is (wet) basis per 100 g and per serving. Food groups with decreasing levels of total phytoestrogens per 100 g are nuts and oilseeds, soy products, cereals and breads, legumes, meat products, and other processed foods that may contain soy, vegetables, fruits, alcoholic, and nonalcoholic beverages. Soy products contain the highest amounts of isoflavone, followed by legumes, meat products and other processed foods, cereals and breads, nuts and oilseeds, vegetables, alcoholic beverages, fruits, and nonalcoholic beverages. Decreasing amounts of lignans are found in nuts and oilseeds, cereals and breads, legumes, fruits, vegetables, soy products, processed foods, alcoholic, and nonalcoholic beverages. The richest sources of specific phytoestrogens, including coumestrol, were identified. The database will improve phytoestrogen intake estimation in future epidemiological and clinical studies particularly in Western populations.     

Phyto-oestrogen intake in Scottish men: use of serum to validate a self-administered food-frequency questionnaire in older men

OBJECTIVE: To study dietary intake and serum concentrations of isoflavones in order to provide relative validation of isoflavone intake estimates from the Scottish Collaborative Group - Food-Frequency Questionnaire (SCG-FFQ). DESIGN: Validation study. SETTING: Southern Scotland. METHOD: Dietary intake of isoflavones was estimated using the semiquantitative SCG-FFQ and rank correlation and Kappa statistics were used for the relative validation of intakes against serum isoflavone concentrations in 203 male participants who were population controls in a case-control study of diet and prostate cancer. RESULTS: The median intake of isoflavones (daidzein and genistein) was 1.0mg/day (l-QR 0.6-1.8). The median serum concentration of genistein was 33.79 nmol/l (I-QR 14.12-64.93), nearly twice that of daidzein (18.00 nmol/l, I-QR 8.26-29.45). Equol was detected in 49% of subjects; in these subjects the median was 0.67 nmol/l (I-QR 0.34-1.51). Isoflavone intake was significantly correlated with serum concentrations of daidzein (p = 0.24, P = 0.001), genistein (p = 0.26, P < 0.001) and total isoflavonoids (sum of daidzein, genistein and equol) ( p = 0.27, P < 0.001). Whereas values for weighted Kappa ranged from 0.16 (P = 0.002) for daidzein and equol combined to 0.22 (P < 0.001) for genistein. CONCLUSIONS: These results demonstrate the suitability of the SCG-FFQ to rank usual isoflavone intakes in older Scottish men, a population observed to have low consumption of soy foods.     

Phytoestrogens and prostate cancer risk

BACKGROUND: Phytoestrogens are natural plant substances. The four main classes are isoflavones, flavonoids, coumestans, and lignans. Phytoestrogens have anti-carcinogenic potential. For evaluation of the effect of phytoestrogens on prostate cancer risk, we reviewed analytical epidemiological data. METHODS: Up to now, there are few studies that have assessed the direct relation between the individual dietary intake of soy products and other nutrients with phytoestrogens and the risk of prostate cancer. We decided to review analytical epidemiological studies providing data on (a) dietary soy intake or flavonoids intake, (b) urinary excretion of isoflavones or lignans, or (c) blood measurements of isoflavones or lignans. Soy is used as a marker for isoflavone intake. RESULTS: Overall, the results of these studies do not show protective effects. Only four of these studies are prospective, and none of them found statistically significant prostate cancer reductions. Two prospective studies measured flavonoid intake and one reported a preventive effect on prostate cancer for the assumption of myricetin. One study assessed enterolactone concentrations in three different countries and showed no reduction in prostate cancer occurrence. CONCLUSION: Few studies showed protective effect between phytoestrogen intake and prostate cancer risk.     

Cruciferous vegetables, genetic polymorphisms in glutathione S-transferases M1 and T1, and prostate cancer risk

Cruciferous vegetables contain anticarcinogenic isothiocyanates (ITCs), particularly the potent sulforaphane, which may decrease risk of prostate cancer through induction of phase II enzymes, including glutathione S-transferases (GSTs). We evaluated this hypothesis in a population-based, case-control study of prostate cancer, including 428 men with incident prostate cancer and 537 community controls. An in-person interview included an extensive food-frequency questionnaire. Genotyping for deletions in GSTM1 and GSTT1 was performed in a subset of men who provided blood. Intakes of cruciferous vegetables and of broccoli, the greatest source of sulforaphane, were associated with decreased prostate cancer risk at all levels above the lowest consumers [adjusted 4th quartile odds ratio (OR)=0.58; 95% confidence interval (CI)=0.38, 0.89, and 0.72 (95% CI=0.49, 1.06)], respectively. In relation to genotypes, there was a nonsignificant increase in risk with the GSTT1 null genotype (OR=1.51; 95% CI=0.98, 2.31) but no effects of GSTM1 genotype. However, men with GSTM1-present genotype and high broccoli intake had the greatest reduction in risk (OR=0.49; 95% CI=0.27, 0.89). Our findings provide evidence that two or more servings per month of cruciferous vegetables may reduce risk of prostate cancer, especially among men with GSTM1-present alleles, and are consistent with a role of dietary ITCs as chemopreventive agents against prostate cancer.