Breast cancer risk in relation to urinary and serum biomarkers of phytoestrogen exposure in the European Prospective into Cancer-Norfolk cohort study

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Introduction Phytoestrogens are a group of compounds found in plants that structurally resemble the hormone oestradiol, and thus have the potential to act as oestrogen agonists or antagonists. Their potential effects may alter the risk of breast cancer, but only a limited range of phytoestrogens has been examined in prospective cohort studies. Methods Serum and urine samples from 237 incident breast cancer cases and 952 control individuals (aged 45 to 75 years) in the European Prospective into Cancer-Norfolk cohort were analysed for seven phytoestrogens (daidzein, enterodiol, enterolactone, genistein, glycitein, o-desmethylangolensin, and equol) using liquid chromatography/mass spectrometry. Data on participants' diet, demographics, anthropometrics, and medical history were collected upon recruitment. All models were adjusted for weight, fat and energy intake, family history of breast cancer, social class, analytical batch, and factors related to oestrogen exposure. Results Urinary or serum phytoestrogens were not associated with protection from breast cancer in the European Prospective into Cancer-Norfolk cohort. Breast cancer risk was marginally increased with higher levels of total urinary isoflavones (odds ratio = 1.08 (95% confidence interval = 1.00 to 1.16), P = 0.055); among those with oestrogen receptor-positive tumours, the risk of breast cancer was increased with higher levels of urinary equol (odds ratio = 1.07 (95% confidence interval = 1.01 to 1.12), P = 0.013). Conclusion There was limited evidence of an association between phytoestrogen biomarkers and breast cancer risk in the present study. There was no indication of decreased likelihood of breast cancer with higher levels of phytoestrogen biomarkers, but the observation that some phytoestrogen biomarkers may be associated with greater risk of breast cancer warrants further study with greater statistical power

Soy intake and breast cancer risk in Singapore Chinese Health Study

We investigated the effects of soy isoflavone intake on breast cancer in a prospective study of 35 303 Singapore Chinese women enrolled during April 1993 to December 1998 in the Singapore Chinese Health Study. At recruitment, each subject was personally administered a validated semiquantitative food frequency questionnaire covering 165 food and beverage items. As of December 31 2005, 629 had developed breast cancer following an accumulation of 338 242 person-years. Using Cox regression and adjusting for age at interview, year of interview, dialect group, education, family history of breast cancer, age when periods became regular, parity, menopausal status, body mass index (BMI), n-3 fatty acid, and other covariates, we found breast cancer risk was reduced significantly in association with high soy intake. Relative to women with lower (below median) soy intake (<10.6 mg isoflavone per 1000 Kcal), women with higher (above median) intake showed a significant 18% risk reduction (relative risk (RR)=0.82, 95% confidence interval (CI)=0.70–0.97). This inverse association was apparent mainly in postmenopausal women (RR=0.74, 95% CI=0.61–0.90), and was not observed in premenopausal women (RR=1.04, 95% CI=0.77–1. 40). Among postmenopausal women, the soy–breast cancer association was stronger in those above median BMI (RR=0.67, 95% CI=0.51–0.88) than in leaner women (RR=0.83, 95% CI=0.62–1.11). Duration of follow-up modified the soy–breast cancer association, the effect being twice as large among women with 10+ vs fewer years of follow-up. Neither oestrogen nor progesterone receptor status of the tumours materially influenced the association. These prospective findings suggest that approximately 10 mg of isoflavones per day, obtained in a standard serving of tofu, may have lasting beneficial effects against breast cancer development

Virgin olive oil as a source of phytoestrogens

In their study of the dietary intake of phytoestrogens in the EPIC cohort, Zamora-Ros et al. do not indicate the contribution that will be made by virgin olive oil. It is understandable that it was difficult to include this in Table 4, as this contribution is very low or zero in non-Mediterranean countries, but it should be mentioned in the text. The mean lignan content of virgin olive oil has been estimated as 2.81 mg/100 ml, pinoresinol being the predominant lignan. In the Greek EPIC cohort, with a mean olive oil intake of 52.0 g/day for men and 44.3 g/day for women, this corresponds to a daily intake of total lignans from olive oil of approximately 1.46 mg and 1.24 mg respectively. This intake of olive oil lignans may contribute to a possible protective effect against ER+ breast cancer in postmenopausal women. It is noteworthy that although most studies of healthy dietary patterns (rich in vegetables) do not show a significant association with breast cancer, it was found that the healthy/Mediterranean pattern, which includes olive oil, was associated with a decreased risk of breast cancer. Moreover, pinoresinol was found to be an important contributor to the protective effect of lignans against postmenopausal breast cancer in the French EPIC cohort. Lignans are of particular public health interest, as they constitute the major phytoestrogen intake in western populations, and although intake of soy isoflavones is high in some countries in the EPIC study, there is no evidence that they have a protective effect against breast cancer in western populations.Peer reviewe

Estimated enterolignans, lignan-rich foods, and fibre in relation to survival after postmenopausal breast cancer

BACKGROUND: Lignans – oestrogenic substances present in various foods – are associated with postmenopausal breast cancer risk, but not much is known regarding their effects on survival. METHODS: In a follow-up study of 2653 postmenopausal breast cancer patients diagnosed between 2001 and 2005, vital status and causes of death were verified through end of 2009. Hazard ratios (HRs) and 95% confidence intervals (CIs) for estimated enterolignans, lignan-rich foods, and dietary fibre in relation to overall survival (OS) and breast cancer-specific survival (BCSS) were assessed using Cox proportional hazards models stratified by age at diagnosis and adjusted for prognostic/confounding factors. RESULTS: Median follow-up time was 6.4 years, and 321 women died, 235 with breast cancer. High estimated enterolactone and enterodiol levels were associated with significantly lower overall mortality (highest quintile, HR=0.60, 95% CI=0.40–0.89, P(Trend)=0.02 and HR=0.63, 95% CI=0.42–0.95, P(Trend)=0.02, respectively). Fibre intake was also associated with a significantly lower overall mortality. Differentiated by median fibre intake, associations with estimated enterolignans were still evident at low but not high fibre intake. There was no effect modification by oestrogen receptor status and menopausal hormone therapy. CONCLUSION: Postmenopausal breast cancer patients with high estimated enterolignans may have a better survival

Red meat, dietary nitrosamines, and heme iron and risk of bladder cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC).

BACKGROUND: Previous epidemiologic studies found inconsistent results for the association between red meat intake, nitrosamines [NDMA: N-nitrosodimethylamine, and ENOC (endogenous nitroso compounds)], and the risk of bladder cancer. We investigated the association between red meat consumption, dietary nitrosamines, and heme iron and the risk of bladder cancer among participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Data on food consumption and complete follow-up for cancer occurrence were available for a total of 481,419 participants, recruited in 10 European countries. Estimates of HRs were obtained by proportional hazard models, stratified by age at recruitment, gender, and study center and adjusted for total energy intake, smoking status, lifetime intensity of smoking, duration of smoking, educational level, and BMI. RESULTS: After a mean follow-up of 8.7 years, 1,001 participants were diagnosed with bladder cancer. We found no overall association between intake of red meat (log2 HR: 1.06; 95% CI: 0.99-1.13), nitrosamines (log2 HR: 1.09; 95% CI: 0.92-1.30 and HR: 0.98; 95% CI: 0.92-1.05 for ENOC and NDMA, respectively) or heme iron (log2 HR: 1.05; 95 CI: 0.99-1.12) and bladder cancer risk. The associations did not vary by sex, high- versus low-risk bladder cancers, smoking status, or occupation (high vs. low risk). CONCLUSIONS: Our findings do not support an effect of red meat intake, nitrosamines (endogenous or exogenous), or heme iron intake on bladder cancer risk

Investigation of circulating metabolites associated with breast cancer risk by untargeted metabolomics: a case–control study nested within the French E3N cohort

BACKGROUND: Perturbations in circulating metabolites prior to a breast cancer diagnosis are not well characterised. We aimed to gain more detailed knowledge to help understand and prevent the disease. METHODS: Baseline plasma samples from 791 breast cancer cases and 791 matched controls from the E3N (EPIC-France) cohort were profiled by nuclear magnetic resonance (NMR)-based untargeted metabolomics. Partial least-squares discriminant analysis (PLS-DA) models were built from NMR profiles to predict disease outcome, and odds ratios and false discovery rate (FDR)-adjusted CIs were calculated for 43 identified metabolites by conditional logistic regression. RESULTS: Breast cancer onset was predicted in the premenopausal subgroup with modest accuracy (AUC 0.61, 95% CI: 0.49-0.73), and 10 metabolites associated with risk, particularly histidine (OR = 1.70 per SD increase, FDR-adjusted CI 1.19-2.41), N-acetyl glycoproteins (OR = 1.53, FDR-adjusted CI 1.18-1.97), glycerol (OR = 1.55, FDR-adjusted CI 1.11-2.18) and ethanol (OR = 1.44, FDR-adjusted CI 1.05-1.97). No predictive capacity or significant metabolites were found overall or for postmenopausal women. CONCLUSIONS: Perturbed metabolism compared to controls was observed in premenopausal but not postmenopausal cases. Histidine and NAC have known involvement in inflammatory pathways, and the robust association of ethanol with risk suggests the involvement of alcohol intake