Emerging evidence suggests that a metabolic profile associated with obesity may be a more relevant risk factor for some cancers than adiposity per se. Basal metabolic rate (BMR) is an indicator of ...overall body metabolism and may be a proxy for the impact of a specific metabolic profile on cancer risk. Therefore, we investigated the association of predicted BMR with incidence of 13 obesity‐related cancers in the European Prospective Investigation into Cancer and Nutrition (EPIC). BMR at baseline was calculated using the WHO/FAO/UNU equations and the relationships between BMR and cancer risk were investigated using multivariable Cox proportional hazards regression models. A total of 141,295 men and 317,613 women, with a mean follow‐up of 14 years were included in the analysis. Overall, higher BMR was associated with a greater risk for most cancers that have been linked with obesity. However, among normal weight participants, higher BMR was associated with elevated risks of esophageal adenocarcinoma (hazard ratio per 1‐standard deviation change in BMR HR1‐SD: 2.46; 95% CI 1.20; 5.03) and distal colon cancer (HR1‐SD: 1.33; 95% CI 1.001; 1.77) among men and with proximal colon (HR1‐SD: 1.16; 95% CI 1.01; 1.35), pancreatic (HR1‐SD: 1.37; 95% CI 1.13; 1.66), thyroid (HR1‐SD: 1.65; 95% CI 1.33; 2.05), postmenopausal breast (HR1‐SD: 1.17; 95% CI 1.11; 1.22) and endometrial (HR1‐SD: 1.20; 95% CI 1.03; 1.40) cancers in women. These results indicate that higher BMR may be an indicator of a metabolic phenotype associated with risk of certain cancer types, and may be a useful predictor of cancer risk independent of body fatness.
What's new?
Although the basal metabolic rate (BMR) – defined as the daily rate of energy metabolism required to preserve vital functions – has been positively associated with increased breast cancer risk, its relevance to other cancers remains unknown. Here, the authors examined associations between predicted BMR and risk of 13 cancers in over 520,000 individuals in Europe. Predicted BMR was generally positively associated with cancer risk. Importantly, among normal weight individuals, BMR was positively associated with cancers of the colon, pancreas, thyroid, esophageal adenocarcinoma, postmenopausal breast, and endometrium, indicating that BMR may identify subgroups of the population who are at greater risk of these malignancies.
Within the PREVIENI project, infertile and fertile women were enrolled from metropolitan, urban and rural Italian areas. Blood/serum levels of several endocrine disrupters (EDs) (perfluorooctane ...sulfonate, PFOS; perfluorooctanoic acid, PFOA; di-2-ethylhexyl-phthalate, DEHP; mono-(2-ethylhexyl)-phthalate, MEHP; bisphenol A, BPA) were evaluated concurrently with nuclear receptors (NRs) gene expression levels (ERa, ERb, AR, AhR, PPARg, PXR) in peripheral blood mononuclear cells (PBMCs). Infertile women from the metropolitan area displayed significantly higher levels of: BPA compared to fertile women (14.9 vs. 0.5 ng/mL serum); BPA and MEHP compared to infertile women from urban and rural areas; enhanced expression levels of NRs, except PPARg. Infertile women from urban and rural areas had PFOA levels significantly higher than those from metropolitan areas. Our study indicates the relevance of the living environment when investigating the exposure to EDs and the modulation of the NR panel in PBMC as a suitable biomarker of the effect, to assess the EDs impact on reproductive health.
The complex etiology of Alzheimer’s disease (AD) prompts scientists to develop multifunctional compounds to combat causes and symptoms of such neurodegeneration. To this aim we designed, synthesized, ...and tested a series of compounds by introducing halophenylalkylamidic functions on the scaffold of AP2238, which is a dual binding site acetylcholinesterase inhibitor. The inhibitory activity was successfully extended to the beta-site amyloid precursor protein cleavage enzyme, leading to the discovery of a potent inhibitor of this enzyme (
3) and affording multifunctional compounds (
2,
6,
8) for the treatment of AD.
Pancreatic cancer (PC) is a highly fatal cancer with currently limited opportunities for early detection and effective treatment. Modifiable factors may offer pathways for primary prevention. In this ...study, the association between the Healthy Lifestyle Index (HLI) and PC risk was examined. Within the European Prospective Investigation into Cancer and Nutrition cohort, 1113 incident PC (57% women) were diagnosed from 400,577 participants followed-up for 15 years (median). HLI scores combined smoking, alcohol intake, dietary exposure, physical activity and, in turn, overall and central adiposity using BMI (HLI
BMI
) and waist-to-hip ratio (WHR, HLI
WHR
), respectively. High values of HLI indicate adherence to healthy behaviors. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and 95% confidence intervals (CI). Sensitivity analyses were performed by excluding, in turn, each factor from the HLI score. Population attributable fractions (PAF) were estimated assuming participants’ shift to healthier lifestyles. The HRs for a one-standard deviation increment of HLI
BMI
and HLI
WHR
were 0.84 (95% CI: 0.79, 0.89; p
trend
= 4.3e−09) and 0.77 (0.72, 0.82; p
trend
= 1.7e−15), respectively. Exclusions of smoking from HLI
WHR
resulted in HRs of 0.88 (0.82, 0.94; p
trend
= 4.9e−04). The overall PAF estimate was 19% (95% CI: 11%, 26%), and 14% (6%, 21%) when smoking was removed from the score. Adherence to a healthy lifestyle was inversely associated with PC risk, beyond the beneficial role of smoking avoidance. Public health measures targeting compliance with healthy lifestyles may have an impact on PC incidence.
Most studies on dietary polyphenol intake and type 2 diabetes (T2D) risk have focused on total or specific subclasses of polyphenols. Since polyphenols are often consumed simultaneously, the joint ...effect of an intake of multiple subclasses should be explored. We aimed to identify profiles of the dietary polyphenol subclasses intake associated with T2D. A total of 60,586 women from the Etude Epidémiologique auprès de femmes de l'Education Nationale (E3N) cohort study were followed for 20 years between 1993 and 2014. T2D cases were identified and validated. The individual energy-adjusted daily intakes of 15 subclasses of polyphenols were estimated at baseline using a food frequency questionnaire and the PhenolExplorer database. We used Bayesian profile regression to perform the clustering of the covariates by identifying exposure profiles of polyphenol intakes and, simultaneously, link these to T2D risk by using multivariable Cox regression models. We validated 2740 incident T2D cases during follow-up, and identified 15 distinct clusters with different intake profiles and T2D risk. When compared to the largest cluster (
= 6298 women), higher risks of T2D were observed in three of those clusters, which were composed of women with low or medium intakes of anthocyanins, dihydroflavonols, catechins, flavonols, hydroxybenzoic acids, lignans, and stilbenes. One cluster (
= 4243), characterized by higher intakes of these polyphenol subclasses, exhibited lower T2D risk when compared to the reference cluster. These results highlight the importance of a varied diet of polyphenol-rich foods such as nuts, fruits, and vegetables to prevent T2D risk.
P53 is a crucial regulator of cell response to DNA damage. MDM4 and MDM2 are the two main negative regulators of p53 activity. Upon DNA damage, their constraint is released and p53 becomes activated ...and exerts its safeguard function by arresting cell growth or by killing excessively damaged cells. Under these conditions, increasing data suggest that MDM4 and MDM2 play novel roles. In this respect, we recently published that MDM4 exerts a positive activity towards p53 mitochondrial apoptosis. We observed that a fraction of MDM4 stably localizes at the mitochondria where upon lethal stress conditions, promotes the mitochondrial localization of p53 phosphorylated at Ser46 (p53Ser46P) and facilitates its binding to BCL2, cytochrome C release and apoptosis. Most importantly, we observed a correlation of MDM4 expression with cisplatin-resistance in a group of human ovarian cancers suggesting that MDM4 proapoptotic activity may have in vivo relevance. Here, we discuss about these and some new findings and compare them with previous data trying to settle some apparent contradictions. In addition, this review discusses the potential relevance of our data to the field of human cancer.
Recent evidence suggests that plant-based diets may reduce the risk of breast cancer (BC). However, the macronutrient composition of plant-based diets and its potential impact on BC risk has not been ...well explored. This analysis investigated the association of macronutrient composition with BC risk across a spectrum of plant-based diet indexes using a multidimensional approach.
This study followed 64,655 participants from the Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale (E3N) cohort from 1993 to 2014. Diets were evaluated using validated 208-item diet history questionnaires at baseline (1993) and follow-up (2005), to calculate adherence to the overall plant-based diet (PDI), healthful plant-based diet (hPDI), and unhealthful plant-based diet (uPDI). The association of macronutrient composition with BC risk was assessed via generalized additive time-dependent Cox models across different levels of these indexes. Response surfaces were generated to visualize compositional associations at the 25th, 50th, and 75th percentile of each index (low, moderate, and high).
A total of 3,932 incident BC cases were identified during the 21-year follow-up. There was a significant association between macronutrient composition and BC risk for hPDI, uPDI, and PDI (all P < 0.001). Akaike information criterion favored the hPDI model for characterizing the association between macronutrients and BC. BC risk was highest for individuals with a lower hPDI score who also consumed a diet containing lower protein (10%), lower carbohydrate (35%), and higher fat (55%). The lowest risk of BC was observed in those with higher hPDI scores with the lowest intake of protein (10%). At higher PDI and uPDI, diets containing higher protein (30%) and fat (45%) had the highest BC risk.
These results demonstrate a complex relationship between macronutrient composition, plant-based diet quality, and BC risk. Further research is needed to examine specific foods that may be driving these associations.
The protocol is registered at clinicaltrials.gov as NCT03285230.
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