Oestrogen exposure and breast cancer risk

Epidemiological and experimental evidence implicates oestrogens in the aetiology of breast cancer. Most established risk factors for breast cancer in humans probably act through hormone-related pathways, and increased concentrations of circulating oestrogens have been found to be strongly associated with increased risk for breast cancer in postmenopausal women. This article explores the evidence for the hypothesis that oestrogen exposure is a major determinant of risk for breast cancer. We review recent data on oestrogens and breast cancer risk, consider oestrogen-related risk factors and examine possible mechanisms that might account for the effects of oestrogen. Finally, we discuss how these advances might influence strategies for reducing the incidence of breast cancer

Diet and risk of diverticular disease in Oxford cohort of European Prospective Investigation into Cancer and Nutrition (EPIC): prospective study of British vegetarians and non-vegetarians

Objective To examine the associations of a vegetarian diet and dietary fibre intake with risk of diverticular disease

Association between physical activity and body fat percentage, with adjustment for BMI:a large cross-sectional analysis of UK Biobank

Objectives The objective of this study was to examine if, in the general population, physically active adults have less body fat after taking body mass index (BMI) into account. Design A cross-sectional analysis of participants recruited into UK Biobank in 2006–2010. Setting UK Biobank assessment centres throughout the UK. Participants 119 230 men and 140 578 women aged 40–69 years, with complete physical activity information, and without a self-reported long-term illness, disability or infirmity. Exposures Physical activity measured as excess metabolic equivalent (MET)-hours per week, estimated from a combination of walking, and moderate and vigorous physical activity. BMI from measured height and weight. Main outcome measure Body fat percentage estimated from bioimpedance. Results BMI and body fat percentage were highly correlated (r=0.85 in women; r=0.79 in men), and both were inversely associated with physical activity. Compared with <5 excess MET-hours/week at baseline, ≥100 excess MET-hours/week were associated with a 1.1 kg/m2 lower BMI (27.1 vs 28.2 kg/m2) and 2.8 percentage points lower body fat (23.4% vs 26.3%) in men, and 2.2 kg/m2 lower BMI (25.6 vs 27.7 kg/m2) and 4.0 percentage points lower body fat (33.9% vs 37.9%) in women. For a given BMI, greater physical activity was associated with lower average body fat percentage (for a BMI of 22.5–24.99 kg/m2: 2.0 (95% CI 1.8 to 2.2), percentage points lower body fat in men and 1.8 (95% CI 1.6 to 2.0) percentage points lower body fat in women, comparing ≥100 excess MET-hours per week with <5 excess MET-hours/week). Conclusions In this sample of middle-aged adults, drawn from the general population, physical activity was inversely associated with BMI and body fat percentage. For people with the same BMI, those who were more active had a lower body fat percentage

The P2X7 Receptor is an Important Regulator of Extracellular ATP Levels

Controlled ATP release has been demonstrated from many neuronal and non-neuronal cell types. Once released, extracellular ATP acts on cells in a paracrine manner via purinergic receptors. Considerable evidence now suggests that extracellular nucleotides, signaling via P2 receptors, play important roles in bone homeostasis modulating both osteoblast and osteoclast function. In this study, we demonstrate that mouse osteoclasts and their precursors constitutively release ATP into their extracellular environment. Levels were highest at day 2 (precursor cells), possibly reflecting the high number of red blood cells and accessory cells present. Mature osteoclasts constitutively released ATP in the range 0.05–0.5 pmol/ml/cell. Both osteoclasts and osteoblasts express mRNA and protein for the P2X7 receptor. We found that in osteoclasts, expression levels are fourfold higher in mature cells relative to precursors, whilst in osteoblasts expression remains relatively constant during differentiation. Selective antagonists (0.1–100 μM AZ10606120, A438079, and KN-62) were used to determine whether this release was mediated via P2X7 receptors. AZ10606120, A438079, and KN-62, at 0.1–10 μM, decreased ATP release by mature osteoclasts by up to 70, 60, and 80%, respectively. No differences in cell viability were observed. ATP release also occurs via vesicular exocytosis; inhibitors of this process (1–100 μM NEM or brefeldin A) had no effect on ATP release from osteoclasts. P2X7 receptor antagonists (0.1–10 μM) also decreased ATP release from primary rat osteoblasts by up to 80%. These data show that ATP release via the P2X7 receptor contributes to extracellular ATP levels in osteoclast and osteoblast cultures, suggesting an important additional role for this receptor in autocrine/paracrine purinergic signaling in bone

Genetic predisposition to metabolically unfavourable adiposity and prostate cancer risk:A Mendelian randomization analysis

BACKGROUND The associations of adiposity with aggressive prostate cancer risk are unclear. Using two-sample Mendelian randomization, we assessed the association of metabolically unfavourable adiposity (UFA), favourable adiposity (FA) and for comparison body mass index (BMI), with prostate cancer, including aggressive prostate cancer. METHODS We examined the association of these genetically predicted adiposity-related traits with risk of prostate cancer overall, aggressive and early onset disease using outcome summary statistics from the PRACTICAL consortium (including 15,167 aggressive cases). RESULTS In inverse-variance weighted models, there was little evidence that genetically predicted one standard deviation higher UFA, FA and BMI were associated with aggressive prostate cancer [OR: 0.85 (95% CI:0.61-1.19), 0.80 (0.53-1.23) and 0.97 (0.88-1.08), respectively]; these associations were largely consistent in sensitivity analyses accounting for horizontal pleiotropy. There was no strong evidence that genetically determined UFA, FA or BMI were associated with overall prostate cancer or early age of onset prostate cancer. CONCLUSIONS We did not find differences in the associations of UFA and FA with prostate cancer risk, which suggest that adiposity is unlikely to influence prostate cancer via the metabolic factors assessed; however, these did not cover some aspects related to metabolic health that may link obesity with aggressive prostate cancer, which should be explored in future studies

Description of the updated nutrition calculation of the Oxford WebQ questionnaire and comparison with the previous version among 207,144 participants in UK Biobank.

PURPOSE: The Oxford WebQ is a web-based 24-h dietary assessment method which has been used in UK Biobank and other large prospective studies. The food composition table used to calculate nutrient intakes has recently been replaced with the UK Nutrient Databank, which has food composition data closer in time to when participants completed the questionnaire, and new dietary variables were incorporated. Here we describe the updated version of the Oxford WebQ questionnaire nutrient calculation, and compare nutrient intakes with the previous version used. METHODS: 207,144 UK Biobank participants completed ≥ 1 Oxford WebQs, and means and standard deviations of nutrient intakes were averaged for all completed 24-h dietary assessments. Spearman correlations and weighted kappa statistics were used to compare the re-classification and agreement of nutrient intakes between the two versions. RESULTS: 35 new nutrients were incorporated in the updated version. Compared to the previous version, most nutrients were very similar in the updated version except for a few nutrients which showed a difference of > 10%: lower with the new version for trans-fat (- 20%), and vitamin C (- 15%), but higher for retinol (+ 42%), vitamin D (+ 26%) and vitamin E (+ 20%). Most participants were in the same (> 60%) or adjacent (> 90%) quintile of intake for the two versions. Except for trans-fat (r = 0.58, κ = 0.42), very high correlations were found between the nutrients calculated using the two versions (r > 0.79 and κ > 0.60). CONCLUSION: Small absolute differences in nutrient intakes were observed between the two versions, and the ranking of individuals was minimally affected, except for trans-fat

Health impacts and environmental footprints of diets that meet the Eatwell Guide recommendations: analyses of multiple UK studies.

OBJECTIVES: To assess the health impacts and environmental consequences of adherence to national dietary recommendations (the Eatwell Guide (EWG)) in the UK. DESIGN AND SETTING: A secondary analysis of multiple observational studies in the UK. PARTICIPANTS: Adults from the European Prospective Investigation into Cancer - Oxford(EPIC-Oxford), UK Biobank and Million Women Study, and adults and children aged 5 and over from the National Diet and Nutrition Survey (NDNS).Primary and secondary outcome measures risk of total mortality from Cox proportional hazards regression models, total greenhouse gas emissions (GHGe) and blue water footprint (WF) associated with 'very low' (0-2 recommendations), 'low' (3-4 recommendations) or 'intermediate-to-high' (5-9 recommendations) adherence to EWG recommendations. RESULTS: Less than 0.1% of the NDNS sample adhere to all nine EWG recommendations and 30.6% adhere to at least five recommendations. Compared with 'very low' adherence to EWG recommendations, 'intermediate-to-high adherence' was associated with a reduced risk of mortality (risk ratio (RR): 0.93; 99% CI: 0.90 to 0.97) and -1.6 kg CO2eq/day (95% CI: -1.5 to -1.8), or 30% lower dietary GHGe. Dietary WFs were similar across EWG adherence groups. Of the individual Eatwell guidelines, adherence to the recommendation on fruit and vegetable consumption was associated with the largest reduction in total mortality risk: an RR of 0.90 (99% CI: 0.88 to 0.93). Increased adherence to the recommendation on red and processed meat consumption was associated with the largest decrease in environmental footprints (-1.48 kg CO2eq/day, 95% CI: -1.79 to 1.18 for GHGe and -22.5 L/day, 95% CI: -22.7 to 22.3 for blue WF). CONCLUSIONS: The health and environmental benefits of greater adherence to EWG recommendations support increased government efforts to encourage improved diets in the UK that are essential for the health of people and the planet in the Anthropocene