phytoestrogens and Adenoma

Epidemiological studies suggest that soya consumption as a source of phyto-oestrogens and isoflavones may be associated with a reduced risk of colorectal cancer. However, findings have not yet been synthesised for all groups of phyto-oestrogens. A meta-analysis was conducted to quantify the association between phyto-oestrogens and colorectal cancer risk. Relevant observational studies published up to June 2016 were identified by searching MEDLINE, EMBASE and Cochrane Library databases. Study-specific relative risks (RR) were pooled in both categorical and dose-response meta-analyses. Out of seventeen identified studies, sixteen were included in the meta-analysis. Comparing the highest with the lowest intake category, inverse associations for phyto-oestrogens overall and by subgroup were observed but were statistically significant in case-controls studies and not in cohort studies. The pooled RR in case-control studies were 0·76 (95 % CI 0·69, 0·84), 0·77 (95 % CI 0·69, 0·85) and 0·70 (95 % CI 0·56, 0·89) for phyto-oestrogens, isoflavones and lignans, respectively, whereas the corresponding pooled RR were 0·95 (95 % CI 0·85, 1·06), 0·94 (95 % CI 0·84, 1·05) and 1·00 (95 % CI 0·64, 1·57) in cohort studies. Dose-response analysis yielded an 8 % reduced risk of colorectal neoplasms for every 20 mg/d increase in isoflavones intake in Asians (pooled RR 0·92; 95 % CI 0·86, 0·97). A non-linear inverse association with colorectal cancer risk was found for lignans intake, but no association for circulating enterolactone concentrations was observed. Thus, study heterogeneity precludes a rigorous conclusion regarding an effect of high exposure to isoflavones on risk of colorectal cancer. Current evidence for an association with lignans exposure is limited. Further prospective studies, particularly evaluating lignans, are warranted to clarify the association between different phyto-oestrogens and colorectal cancer risk.

Topics: Adenoma; Animals; Colorectal Neoplasms; Diet, Healthy; Evidence-Based Medicine; Female; Functional Food; Humans; Incidence; Isoflavones; Lignans; Male; Observational Studies as Topic; Phytoestrogens; Reproducibility of Results; Risk; Sex Factors; Soy Foods

To assess the safety and effect of the supplementation of a patented blend of dietary phytoestrogens and insoluble fibers on estrogen receptor (ER)-β and biological parameters in sporadic colonic adenomas.. A randomized, double-blind placebo-controlled trial was performed. Patients scheduled to undergo surveillance colonoscopy for previous sporadic colonic adenomas were identified, and 60 eligible patients were randomized to placebo or active dietary intervention (ADI) twice a day, for 60 d before surveillance colonoscopy. ADI was a mixture of 175 mg milk thistle extract, 20 mg secoisolariciresinol and 750 mg oat fiber extract. ER-β and ER-α expression, apoptosis and proliferation (Ki-67 LI) were assessed in colon samples.. No adverse event related to ADI was recorded. ADI administration showed a significant increases in ER-β protein (0.822 ± 0.08 vs 0.768 ± 0.10, P = 0.04) and a general trend to an increase in ER-β LI (39.222 ± 2.69 vs 37.708 ± 5.31, P = 0.06), ER-β/ER-α LI ratio (6.564 ± 10.04 vs 2.437 ± 1.53, P = 0.06), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (35.592 ± 14.97 vs 31.541 ± 11.54, P = 0.07) and Ki-67 (53.923 ± 20.91 vs 44.833 ± 10.38, P = 0.07) approximating statistical significance. A significant increase of ER-β protein (0.805 ± 0.13 vs 0.773 ± 0.13, P = 0.04), mRNA (2.278 ± 1.19 vs 1.105 ± 1.07, P < 0.02) and LI (47.533 ± 15.47 vs 34.875 ± 16.67, P < 0.05) and a decrease of ER-α protein (0.423 ± 0.06 vs 0.532 ± 0.11, P < 0.02) as well as a trend to increase of ER-β/ER-α protein in ADI vs placebo group were observed in patients without polyps (1.734 ± 0.20 vs 1.571 ± 0.42, P = 0.07).. The role of ER-β on the control of apoptosis, and its amenability to dietary intervention, are supported in our study.

Topics: Adenoma; Aged; Apoptosis; Biomarkers; Biopsy; Cell Proliferation; Colonic Neoplasms; Colonic Polyps; Colonoscopy; Diet; Dietary Supplements; Double-Blind Method; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Male; Microscopy, Fluorescence; Middle Aged; Phytoestrogens

Topics: Adenoma; Aspirin; Colorectal Neoplasms; Estrogen Receptor alpha; Estrogen Receptor beta; Humans; Ligands; Lignin; Metformin; Phytoestrogens; Silymarin

Genistein is a naturally occurring isoflavone that interacts with estrogen receptors and multiple other molecular targets. Human exposure to genistein is predominantly through consumption of soy products, including soy-based infant formula and dietary supplements. Consumption of soy and genistein has been associated with a variety of beneficial effects in animals and humans, but concerns have also been raised concerning potential adverse effects of genistein, particularly with regard to reproductive toxicity and the induction or potentiation of carcinogenesis, due primarily to its weak estrogenic activity. Because of these concerns, genistein was selected as one of the compounds to be examined in a protocol utilizing Sprague-Dawley rats to evaluate the effects of multigenerational and long-term exposures to doses of estrogenic agents that produce subtle reproductive tract lesions in developmentally exposed Sprague-Dawley rat pups. Results from the multigenerational reproductive toxicology feed study are reported in this report, and results of the 2-year feed study are reported separately (NTP, 2008a). Data from a preliminary reproductive dose range-finding feed study (NTP, 2007) that utilized exposure concentrations of up to 1,250 ppm genistein were used to select dietary exposure concentrations of 0, 5, 100, and 500 ppm for the current study. These dietary doses resulted in ingested genistein doses of approximately 0, 0.3, 7, or 35 mg genistein/kg body weight per day for males and 0, 0.5, 10, or 51 mg/kg per day for females during the time that the rats were directly consuming dosed feed. The current study was a multigenerational study (F(0) through F(4), with F(5) litters terminated at weaning) focused on reproductive endpoints. Animals were continuously exposed to genistein from the time that the F(0) generation was 6 weeks old through weaning of the F(3) generation, and animals of the F(0) through F(4) generations were sacrificed and necropsied on postnatal day 140 (PND 140). Dosed feed was removed from the F(3) pups at the time of weaning, and this generation and subsequent generations were maintained on control feed for the remainder of the study. For this study, 140 animals of each sex were obtained from the NCTR CD (Sprague-Dawley) rat colony at weaning and placed on a soy- and alfalfa-free diet that was used throughout the study in an attempt to maintain consistently low background exposure to phytoestrogens. Thirty-five animals per sex were assi

Topics: Adenocarcinoma; Adenoma; Animals; Carcinogens; Female; Genistein; Male; Mammary Neoplasms, Animal; Neoplasms, Experimental; Phytoestrogens; Pituitary Neoplasms; Pregnancy; Rats; Rats, Sprague-Dawley; Recovery of Function; Reproduction; Toxicity Tests, Chronic; Withholding Treatment

The mammalian lignan enterolactone (ENL) produced from plant lignans, e. g. secoisolariciresinol diglycoside (SDG), may protect against various cancers in humans. The present work aims to evaluate the effect of flaxseed on tumour formation in multiple intestinal neoplasia (Min) mice, a model for colon tumorigenesis.. Male and female Min mice were fed either with a non-fibre control diet or the same diet supplemented with 0.5 % (w/w) defatted flaxseed meal. Conversion of SDG to the mammalian lignans enterodiol (END) and ENL in the gut, and plasma ENL, were measured by HPLC with coulometric electrode array detector (CEAD) and timeresolved fluoroimmunoassay, respectively. Wild-type mice were also fed with the experimental diets in order to see whether lignan metabolism is different in Min and wild-type mice.. The total number of adenomas or their size in the small intestine was not different in the flaxseed and control groups. The flaxseed group had a tendency for a decreased number of colon adenomas in both genders. Gender and genotype based differences were found in the intestinal ENL levels. When compared to Min females, Min males in the flaxseed group had several fold higher ENL levels in the small intestine (Min males 125 +/- 124.5 nmol/g vs. females 22.8 +/- 16.0 nmol/g, P = 0.048) and caecum (47.6 +/- 31.6 nmol/g vs. females 14.5 +/- 6.6 nmol/g, P = 0.001). Presence of adenomas in the gut influences the intestinal lignan metabolism. Min mice had less intestinal END and ENL as compared with the wild-type mice (P < 0.05). Mean plasma ENL increased 7-fold during the flaxseed feeding (7 nmol/L in control vs. 50 nmol/L in flaxseed group) but no differences between gender and genotype were found. The plasma ENL level did not correlate with adenoma number in the small intestine and colon.. The number of intestinal adenomas in the Min mouse model is not related to ENL level in plasma nor is it associated with the levels of intestinal lignans. A gender difference in ENL lignan metabolism was found in the gut but not in the plasma.

Topics: Adenoma; Animals; Chromatography, High Pressure Liquid; Disease Models, Animal; Female; Flax; Fluoroimmunoassay; Genotype; Intestinal Neoplasms; Lignans; Male; Mice; Mice, Mutant Strains; Neoplasms, Multiple Primary; Phytoestrogens; Random Allocation; Sex Factors