Prosbiotate: a multicenter, prospective analysis of infectious complications after prostate biopsy.

PURPOSE: Prostate biopsy side effects have a role in the controversy over screening for prostate cancer. We measured the precise incidence of infection after prostate biopsy and determined risk factors. MATERIALS AND METHODS: We performed a prospective, multicenter study in France from April to June 2013. All prostate biopsies done during this period were included in study. A web based questionnaire was used to identify patient characteristics, biopsy methods and postoperative infectious episodes. External audit helped ensure data completeness. The primary outcome was the post-biopsy infection rate. We determined risk factors for infectious complications using univariate and multivariate analysis. RESULTS: The study included 2,718 patients, of whom 6% reported receiving antibiotics in the previous 6 months and 7.4% had a history of prostatitis. Recommended antibiotic prophylaxis consisting of 2 fluoroquinolone tablets 2 hours before examination for prostate biopsy was noted in 78.3% of cases. Post-biopsy sepsis was found in 76 subjects (2.8%). On multivariate analysis predictors of post-biopsy sepsis were noncompliance with antibiotic prophylaxis guidelines (OR 2.3, 95% CI 1.4-3.9, p = 0.001), antibiotic treatment in the previous 6 months (OR 2.1, 95% CI 1.1-3.9, p = 0.015) and a history of prostatitis (OR 1.7, 95% CI 1.2-2.4, p = 0.002). CONCLUSIONS: In this study the incidence of post-prostate biopsy sepsis was 2.8% and no deaths were reported. Risk factors identified on multivariate analysis were noncompliance with antibiotic prophylaxis according to guidelines, antibiotic treatment in the previous 6 months and a history of prostatitis.

The association between histone 3 lysine 27 trimethylation (H3K27me3) and prostate cancer: relationship with clinicopathological parameters.

BACKGROUND: It is well established that genetic and epigenetic alterations are common events in prostate cancer, which may lead to aberrant expression of critical genes. The importance of epigenetic mechanisms in prostate cancer carcinogenesis is increasingly evident. In this study, the focus will be on histone modifications and the primary objectives are to map H3K27me3 marks and quantify RAR beta 2, ER alpha, SRC3, RGMA, PGR, and EZH2 gene expressions in prostate cancer tissues compared to normal tissues. In addition, a data analysis was made in connection with the clinicopathological parameters. METHODS: 71 normal specimens and 66 cancer prostate tissues were randomly selected in order to assess the proportion of the repressive H3K27me3 mark and gene expression. H3K27me3 level was evaluated by ChIP-qPCR and mRNA expression using RT-qPCR between prostate cancer and normal tissues. Subsequently, western-blotting was performed for protein detection. The analysis of variance (ANOVA) was performed, and Tukey's test was used to correct for multiple comparisons (p-value threshold of 0.05). The principal component analysis (PCA) and discriminant factorial analysis (DFA) were used to explore the association between H3K27me3 level and clinicopathological parameters. RESULTS: The study demonstrated that H3K27me3 level was significantly enriched at the RAR beta 2, ER alpha, PGR, and RGMA promoter regions in prostate cancer tissues compared to normal tissues. After stratification by clinicopathological parameters, the H3K27me3 level was positively correlated with Gleason score, PSA levels and clinical stages for RAR beta 2, ER alpha, PGR, and RGMA. High H3K27me3 mark was significantly associated with decreased RAR beta 2, ER alpha, PGR and RGMA gene expressions in prostate cancer sample compared to the normal one. Moreover, the results showed that mRNA level of EZH2, AR and SRC3 are upregulated in prostate cancer compared to normal prostate tissues and this correlates positively with Gleason score, PSA levels and clinical stages. Obviously, these observations were confirmed by protein level using western-blot. CONCLUSIONS: This data clearly demonstrated that H3K27me3 level correlated with aggressive tumor features. Also this study revealed that reverse correlation of RAR beta 2, ER alpha, PGR, and RGMA expressions with EZH2, SRC3, and AR expressions in prostate cancer tissues suggests that these genes are the target of EZH2. Therefore, all therapeutic strategies leading to histone demethylation with epigenetic drugs such as histone methyltransferase inhibitor may be relevant treatments against prostate cancer.

Comparative effects of soy phytoestrogens and 17ß-estradiol on DNA methylation of a panel of 24 genes in prostate cancer cell lines.

Major phytoestrogens genistein and daidzein have been reported to have the ability to reverse DNA methylation in cancer cell lines. The mechanism by which genistein and daidzein have an inhibiting action on DNA methylation is not well understood. The aim of this study was to investigate the effects of soy phytoestrogens and the natural estrogen 17ß-estradiol (E2) to determine whether one of the estrogen receptors is mobilized for the action of these compounds on DNA methylation. We also made a comparative study with a DNA methylation inhibitor (5-azacytidine) and a DNA methylation activator (budesonide). Three prostate cell lines, PC-3, DU-145, and LNCaP, were treated with 40 µM genistein, 110 µM daidzein, 2 µM budesonide, 2 µM 5-azacytidine, and 10 µM E2. In these 3 human prostate cancer cell lines, we performed methylation quantification using methyl-profiler-DNA-methylation analysis. Soy phytoestrogens and E2 induced a demethylation of all the promoter regions studied except for those that were unmethylated in control cells. Our results showed that E2 induces, like soy phytoestrogen, a decrease in DNA methylation in prostate cancer cell lines. This action may be mediated through ERß.

Soy phytoestrogens modify DNA methylation of GSTP1, RASSF1A, EPH2 and BRCA1 promoter in prostate cancer cells.

BACKGROUND: The aim of this study was to determine the effects of soy phytoestrogens on the methylation of promoter genes in prostate tumors. The incidence of prostate cancer in Asia is thirty percent lower than in Western countries. Since soy phytoestrogens represent a large portion of the Asian diet, evidence suggests their protective effect against prostate cancer. MATERIALS AND METHODS: In three human prostate cancer cell lines, methylation-specific-PCR was used to determine the effect of soy isoflavones (genistein and daidzein), compared to known demethylating agent 5-azacytidine as control in the promoter regions of glutathione S-transferase P1 (GSTP1), Ras association domain family 1 (RASSF1A), ephrin B2 (EPHB2) and breast cancer 1 (BRCA1) genes. In parallel, immunohistochemistry was used to assess the effects of genistein, daidzein and 5-azacytidine treatment on the corresponding protein expression. RESULTS: All studied promoters, with the exception of that for BRCA1, were strongly methylated without treatment. After treatment by phytoestrogens, demethylation of GSTP1 and EPHB2 promoter regions was observed and an increase in their protein expression was demonstrated by immunohistochemistry. CONCLUSION: Epigenetic modifications of DNA, such as the promoter CpG island demethylation of tumor suppressor genes, might be related to the protective effect of soy on prostate cancer.

Genetic polymorphisms in CYP1A1, CYP1B1, COMT, GSTP1 and NAT2 genes and association with bladder cancer risk in a French cohort.

UNLABELLED: Tobacco smoking and environmental exposures are the main known risk factors for bladder cancer (BC) via exposure to chemical carcinogens. Genetic differences in the metabolism of chemicals have been suggested to be associated with individual susceptibility to BC. Polymorphisms in genes coding to metabolising enzymes, resulting in variation of carcinogen detoxification efficiency, may therefore change the response of individuals to chemical carcinogens and be associated with an increased BC risk. PATIENTS AND METHODS: The aim of the study was to investigate the association between functional polymorphisms in CYP1A1, CYP1B1, COMT, GSTP1 and NAT2 genes and BC risk, through a hospital-based case-control study. The genotyping of 11 Single Nucleotide Polymorphisms (SNPs) was carried out on DNA of 51 bladder cancer male patients and 45 male controls. The technique of MGB (Minor Groove Binder) probes that utilize allelic discrimination with the Taqman(R) method was used. RESULTS: Individuals with NAT2 slow acetylator genotypes had a significant increase in risk of BC compared to individuals with NAT2 rapid acetylators (OR adjusted for smoking status=2.70; 95% CI, 1.10-6.61). GSTP1 Ile(105)Val variants (deletion of one - Ile/Val- and two -Val/Val-, null genotype- copies) showed a marginal increased risk of BC with OR adjusted for smoking status of 2.27 (95% CI, 0.97-5.31) compared to individuals carrying wild-type genotype (Ile/Ile). No statistically significant effects on BC risk with CYP1A1, CYP11B1 and COMT genotypes were observed. CONCLUSION: The results are consistent with previous literature among Caucasian populations.

Methylation analysis of BRCA1, RASSF1, GSTP1 and EPHB2 promoters in prostate biopsies according to different degrees of malignancy.

Prostate cancer is the most common cancer among men and the second leading cause of cancer-related deaths in the United States. CpG island methylation causes gene silencing and could be decisive in prostate carcinogenesis and progression. Its role was investigated at multiple gene sites during prostate carcinogenesis. Methylation-specific polymerase chain reaction (MS-PCR) was used to analyze 4 interest gene promoter status in 12 patients with adenocarcinoma, 7 patients with prostate intraepithelial neoplasia, 3 patients with peritumor tissues and 15 healthy patients, so a total of 37 prostate biopsy samples constituted the cohort of the study. Despite the biopsy histology, the results have confirmed that BRCA1, RASSF1, GSTP1 and EPHB2 promoter methylation was found in each sample, except two.

Immunohistochemical staining of mucin 1 in prostate tissues.

UNLABELLED: Prostate cancer is a major public health problem in the world. Molecular studies are necessary for the development of prognostic markers in prostate cancer. There is a great interest in mucin studies in treatment development of human malignancies, including prostate cancer. Nevertheless, their expressions in prostate cancer need further investigation. MATERIALS AND METHODS: Mucin 1 (MUC1) expression was examined in 100 prostate biopsies and were compared with prostate carcinoma cell lines (DU-145, PC-3, LNCaP) by immunohistochemistry. RESULTS: Biopsies were healthy, tumor, peritumor or presented an intraepithelial neoplasia. Staining of MUC1 was exihibited in PC-3 cells, was higher in DU-145, and was not expressed by LNCaP. Tumor sections presented more positive expression of MUC1 than non-tumor sections. CONCLUSION: MUC1 expression is correlated with the histological degree of malignancy.

Orally administered isoflavones are present as glucuronides in the human prostate.

Better knowledge of the bioavailability and metabolism of isoflavones in prostate tissue is needed to further investigate their mechanisms of action in the context of prostate cancer prevention. A total of 12 men with benign prostatic hyperplasia received soy extract supplementation (3 Evestrel capsules, providing a total of 112.5 mg isoflavones aglycone eq/day) for 3 days before prostate surgery. Blood and prostate tissues were sampled and metabolites were identified using electrospray ionization liquid chromatography tandem mass spectrometry (LC-ESI-MS/MS) and chemically synthesized standards of glucuronidated isoflavones. The main metabolites were the same in prostate tissue and in plasma, namely, 2 monoglucuronides of daidzein and 2 monoglucuronides of genistein. Concentrations of total isoflavones measured in prostate reached 1.05 +/- 0.62 nmol/g tissue (range 0.30-2.23) at the time of sampling, 12 h after the last isoflavone supplementation. At that time point, prostate concentrations were lower than plasma concentrations in all volunteers: 0.47 nmol/g vs. 0.66 microM for daidzein and 0.58 nmol/g vs. 0.78 microM for genistein. Isoflavone mechanisms of action should thus be investigated in in vitro cell studies using physiological conditions, intracellular concentrations below 5 nmol/g and no intracellular deconjugation of the monoglucuronide metabolites.

DNA repair gene ERCC2, XPC, XRCC1, XRCC3 polymorphisms and associations with bladder cancer risk in a French cohort.

In polygenic diseases, association studies look for genetic variation such as polymorphisms in low penetrance genes, i.e. genes in interaction with environmental factors. DNA repair systems that protect the genome from deleterious endogenous and exogenous damage have been shown to significantly reduce activity. In particular, enzymes of the nucleotide excision repair pathway are suspected to be implicated in cancer. In this study bladder cancer which is viewed as a polygenic disease was investigated. The functional polymorphisms of four DNA repair genes, excision repair cross-complementing group 2 (ERCC2), Xeroderma Pigmentosum group C (XPC), and Xray repair cross-complementing groups 1 and 3 (XRCC1 and XRCC3) were analyzed. The studied population included 51 bladder cancer cases and 45 controls. The genotyping of six SNP (single nucleotide polymorphism) was carried out on these populations with the MGB (Minor Groove Binder) probe technique which uses allelic discrimination with the Taqman method. The Gln allele of the XPC 939 polymorphism was found to be associated with an increase in bladder cancer risk.

Palliative transarterial embolization of renal tumors in 20 patients.

OBJECTIVES: The aim of this study is to evaluate immediate technical and clinical results of palliative transarterial renal embolization in patients with symptomatic renal tumors. METHODS: Parenchymal embolization of 20 renal tumors was performed in 20 symptomatic patients with hematuria and/or lumbar pain and/or para-neoplastic syndrome. Seven patients were inoperable because of poor general condition, and 15 patients had metastatic lesions. RESULTS: Immediate technical success was observed, with post-infarction pain in all patients requiring analgesia in 12 cases (which was successful in 90%); 8 patients had transitory fever. With a median follow up of 8.1 (range 4-27) months, recurrent hematuria was noted in two patients for which partial embolization was initially chosen; pain did not recur in any patients. CONCLUSIONS: Palliative embolization of advanced symptomatic renal tumors is easy to accomplish with low morbidity. It helps to alleviate invalidating symptoms in a multidisciplinary management of advanced renal tumors.

[Giant ureterohydronephrosis of the lower segment due to obstructive megaureter in a context of ureteropelvic duplication]. / Urétérohydronéphrose géante du système inférieur par méga-uretère obstructif sur duplicité pyélo-urétérale.

Ureterohydronephrosis of the lower segment in a context of ureteric duplication is a rare entity and is usually associated with vesicoureteric reflux. The authors report the case of a 35-year-old woman with giant ureterohydronephrosis of the lower segment secondary to partial ureteric duplication due to primary megaureter discovered in a context of infection. After primary percutaneous drainage of the collection, treatment consisted of partial nephrectomy with preservation of the good quality upper segment.

Genome-wide DNA methylation modified by soy phytoestrogens: role for epigenetic therapeutics in prostate cancer?

In prostate cancer, DNA methylation is significantly associated with tumor initiation, progression, and metastasis. Previous studies have suggested that soy phytoestrogens might regulate DNA methylation at individual candidate gene loci and that they play a crucial role as potential therapeutic agents for prostate cancer. The purpose of our study was to examine the modulation effects of phytoestrogens on a genome-wide scale in regards to DNA methylation in prostate cancer. Prostate cancer cell lines DU-145 and LNCaP were treated with 40 µM of genistein and 110 µM of daidzein. DNMT inhibitor 5-azacytidine (2 µM) and the methylating agent budesonide (2 µM) were used to compare their demethylation/methylation effects with phytoestrogens. The regulatory effects of phytoestrogens on DNA methylation were analyzed by using a methyl-DNA immunoprecipitation method coupled with Human DNA Methylation Microarrays (MeDIP-chip). We observed that the methylation profiles of 58 genes were altered by genistein and daidzein treatments in DU-145 and LNCaP prostate cancer cells. In addition, the methylation frequencies of the MAD1L1, TRAF7, KDM4B, and hTERT genes were remarkably modified by genistein treatment. Our results suggest that the modulation effects of phytoestrogens on DNA methylation essentially lead to inhibition of cell growth and induction of apoptosis. Genome-wide methylation profiling reported here suggests that epigenetic regulation mechanisms and, by extension, epigenetics-driven novel therapeutic candidates warrant further consideration in future "omics" studies of prostate cancer.

Prostate cancer: The main risk and protective factors-Epigenetic modifications.

With 13 million new cases worldwide every year, prostate cancer is as a very real public health concern. Prostate cancer is common in over-50s men and the sixth-leading cause of cancer-related death in men worldwide. Like all cancers, prostate cancer is multifactorial - there are non-modifiable risk factors like heredity, ethnicity and geographic location, but also modifiable risk factors such as diet. Diet-cancer linkages have risen to prominence in the last few years, with accruing epidemiological data pointing to between-population incidence differentials in numerous cancers. Indeed, there are correlations between fat-rich diet and risk of hormone-dependent cancers like prostate cancer and breast cancer. Diet is a risk factor for prostate cancer, but certain micronutrients in specific diets are considered protective factors against prostate cancer. Examples include tomato lycopene, green tea epigallocatechin gallate, and soy phytoestrogens. These micronutrients are thought to exert cancer-protective effects via anti-oxidant pathways and inhibition of cell proliferation. Here, we focus in on the effects of phytoestrogens, and chiefly genistein and daidzein, which are the best-researched to date. Soy phytoestrogens are nonsteroid molecules whose structural similarity lends them the ability to mimic the effects of 17ß-estradiol. On top of anti-oxidant effects, there is evidence that soy phytoestrogens can modulate the epigenetic modifications found in prostate cancer. We also studied the impact of phytoestrogens on epigenetic modifications in prostate cancer, with special focus on DNA methylation, miRNA-mediated regulation and histone modifications.

[Pyelo-ureteric amyloidosis]. / Amylose pyélo-urétérale.

The authors report a case of urinary tract amyloidosis in a 55-year-old woman with no particular medical history. In the light of this original case, the authors present a review of the pathophysiology, diagnosis, histology and treatment of this disease. A review of the literature confirms the rarity of this entity and its variable clinical expression. An aetiological work-up must always be performed, as amyloidosis can be the complication of numerous diseases.

[Compression of the bulbar urethra by transobturator suburethral tape: anatomical study]. / Compression de l'urèthre bulbaire par bandelette sous uréthrale trans-obturatrice: étude anatomique.

INTRODUCTION: The management of female stress urinary incontinence has been markedly improved by the suprapubic tension-free vaginal tape (TVT) and transobturator tape techniques. The objective of our study was to assess the feasibility of this type of technique in males based on cadavre dissection. MATERIAL AND METHOD: A 300 mm x 15 mm polypropylene tape was inserted via a transobturator approach on a cadavre stored in the refrigerator at 4 degrees C and on three cadavres stored in formalin. The technique was almost identical to that used in females. It requires a midline perineal incision in the raphe and two small lateral incisions. The deep transverse muscle of the perineum was opened with scissors. The needle was introduced via the lateral incisions and its progression was guided by a finger introduced into the perineal orifice. The cadavre was then sectioned sagittally to verify the course of the tape and its relations to adjacent structures. RESULTS: The operative technique did not raise any particular problems. Dissection revealed that the tape crossed the deep transverse muscle of the perineum and the levator ani muscle, before travelling towards the obturator foramen. The tape avoided the bladder, prostate, corpora cavernosa, and pudendal pedicle. CONCLUSION: The transobturator tape technique therefore appears to be feasible in males. It does not appear to comprise any particular risks for adjacent organs. This anatomical study appeared to be essential before considering an in vivo application.

[Post-traumatic secondary arteriovenous fistulae of the kidney and their embolization. Report of 3 cases]. / Fistules artério-veineuses secondaires post-traumatiques du rein et leur embolisation. A propos de 3 cas.

INTRODUCTION: Non-iatrogenic post-traumatic arteriovenous fistulas of the kidney raise a diagnostic and especially therapeutic problems. The authors report their experience based on 3 cases of arteriovenous fistulas treated by selective embolization during diagnostic arteriography. MATERIALS AND METHOD: In a series of 18 patients urgently admitted to hospital for kidney trauma during 2000, 3 patients presented a secondary arteriovenous fistula diagnosed on arteriography. All patients were initially treated by surveillance in the surgical ward. The diagnosis of arteriovenous fistula was subsequently suspected following recurrence of haematuria with a moderate fall in haemoglobin in two cases, and secondary appearance of lumbar pain without anaemia in the third case. For the two patients with secondary haematuria, arteriography demonstrated an arteriovenous fistula associated with an arterio-caliceal fistula. For the last patient, Doppler ultrasound suggested the diagnosis of arteriovenous fistula, which was confirmed by the arteriography. RESULTS: Selective embolization by "coils" and particle was performed during arteriography and ensured closure of the fistulas in every case. The postoperative course was uneventful for all three patients. With a mean follow-up of 7 months, no recurrence of the fistula has been observed. The remaining renal parenchyma is functional with preservation of renal function. CONCLUSION: The risk of arteriovenous fistula must be kept in mind in any case of lumbar trauma. Arteriography with selective embolization allows good control of these secondary fistulas while preserving a maximum of functional renal parenchyma, and therefore appears to be the treatment of choice of this complication.

Epigenetic modifications in prostate cancer.

Prostate cancer is the most common cancer in men and the second leading cause of cancer deaths in men in France. Apart from the genetic alterations in prostate cancer, epigenetics modifications are involved in the development and progression of this disease. Epigenetic events are the main cause in gene regulation and the three most epigenetic mechanisms studied include DNA methylation, histone modifications and microRNA expression. In this review, we summarized epigenetic mechanisms in prostate cancer. Epigenetic drugs that inhibit DNA methylation, histone methylation and histone acetylation might be able to reactivate silenced gene expression in prostate cancer. However, further understanding of interactions of these enzymes and their effects on transcription regulation in prostate cancer is needed and has become a priority in biomedical research. In this study, we summed up epigenetic changes with emphasis on pharmacologic epigenetic target agents.

Genistein and daidzein: different molecular effects on prostate cancer.

Diet is believed to play an important role in cancer. It has been revealed by epidemiological studies that Asian populations, who consume phytoestrogens in large amounts, have a lower incidence of prostate cancer in comparison with the Western world, where consumption of soy is lower. Genistein and daidzein, the soy phytoestrogens most widely studied, are believed to be potent anticancer agents and have been shown to possess anticancer properties. It has been shown that these compounds inhibit the growth of cancer cells through the modulation of genes controlling cell-cycle progression. Genistein inhibits the activation of the kappa light polypeptide gene enhancer in B-cells (NF-κB), signaling pathway, which is implicated in the balance between cell survival and programmed cell death (apoptosis). Antioxidant and antiangiogenesis properties of genistein have been also described. Soy isoflavones are also implicated in reversion of epigenetic events observed in prostate cancer. Significant advances have been made for understanding how soy isoflavones are implicated in protection against prostate cancer. However, more studies are needed to better-understand and elucidate all pathways mobilized by genistein and daidzein, in order to fully exploit their anticancer properties.

Gene panel model predictive of outcome in patients with prostate cancer.

In men at high risk for prostate cancer, established clinical and pathological parameters provide only limited prognostic information. Here we analyzed a French cohort of 103 prostate cancer patients and developed a gene panel model predictive of outcome in this group of patients. The model comprised of a 15-gene TaqMan Low-Density Array (TLDA) card, with gene expressions compared to a standardized reference. The RQ value for each gene was calculated, and a scoring system was developed. Summing all the binary scores (0 or 1) corresponding to the 15 genes, a global score is obtained between 0 and 15. This global score can be compared to Gleason score (0 to 10) by recalculating it into a 0-10 scaled score. A scaled score ≥2 suggested that the patient is suffering from a prostate cancer, and a scaled score ≥7 flagged aggressive cancer. Statistical analyses demonstrated a strongly significant linear correlation (p=3.50E-08) between scaled score and Gleason score for this prostate cancer cohort (N=103). These results support the capacity of this designed 15 target gene TLDA card approach to predict outcome in prostate cancer, opening up a new avenue for personalized medicine through future independent replication and applications for rapid identification of aggressive prostate cancer phenotypes for early intervention.

DNA methylation and soy phytoestrogens: quantitative study in DU-145 and PC-3 human prostate cancer cell lines.

AIM: DNA hypermethylation is an epigenetic mechanism which induces silencing of tumor-suppressor genes in prostate cancer. Many studies have reported that specific components of food plants like soy phytoestrogens may have protective effects against prostate carcinogenesis or progression. Genistein and daidzein, the major phytoestrogens, have been reported to have the ability to reverse DNA hypermethylation in cancer cell lines. The aim of this study was to investigate the potential demethylating effects of these two soy compounds on BRCA1, GSTP1, EPHB2 and BRCA2 promoter genes. METHODS & MATERIALS: Prostate cell lines DU-145 and PC-3 were treated with genistein 40 µM, daidzein 110 µM, budesonide (methylating agent) 2 µM and 5-azacytidine (demethylating agent) 2 µM. In these two human prostate cancer cell lines we performed methylation quantification by using Methyl Profiler DNA methylation analysis. This technique is based on a methylation-specific digestion followed by quantitative PCR. We analyzed the corresponding protein expression by western blotting. RESULTS: Soy phytoestrogens induced a demethylation of all promoter regions studied except for BRCA2, which is not methylated in control cell lines. An increase in their protein expression was also demonstrated by western blot analysis and corroborated the potential demethylating effect of soy phytoestrogens. CONCLUSION: This study showed that the soy phytoestrogens, genistein and daidzein, induce a decrease of methylation of BRCA1, GSTP1 and EPHB2 promoters. Therefore, soy phytoestrogens may have a protective effect on prostate cancer. However, more studies are needed in order to understand the mechanism by which genistein and daidzein have an inhibiting action on DNA methylation.