The application of causal mediation analysis (CMA) considering the mediation effect of a third variable is increasing in epidemiological studies; however, this requires fitting strong assumptions on ...confounding bias. To address this limitation, we propose an extension of CMA combining it with Mendelian randomization (MRinCMA). We applied the new approach to analyse the causal effect of obesity and diabetes on pancreatic cancer, considering each factor as potential mediator. To check the performance of MRinCMA under several conditions/scenarios, we used it in different simulated data sets and compared it with structural equation models. For continuous variables, MRinCMA and structural equation models performed similarly, suggesting that both approaches are valid to obtain unbiased estimates. When noncontinuous variables were considered, MRinCMA presented, overall, lower bias than structural equation models. By applying MRinCMA, we did not find any evidence of causality of obesity or diabetes on pancreatic cancer. With this new methodology, researchers would be able to address CMA hypotheses by appropriately accounting for the confounding bias assumption regardless of the conditions used in their studies in different settings.
The aim of this study was to evaluate whether dietary behaviours of the Spanish adult population were changed during the COVID-19 outbreak confinement. For that purpose, an online questionnaire, ...based on 44 items including socio-demographic data, Mediterranean diet (MedDiet) Adherence Screener (MEDAS) as a reference of a healthy diet, processed foods intake, changes in their usual food choices and weight gain was distributed using social media and snowball sampling. A total of 7514 participants (37% aged below 35 years, 70.6% female, 77.9% university-level education or higher) from all the Spanish territory completed the questionnaire. Results outlined healthier dietary behaviours during the confinement when compared to previous habits. Overall, the MEDAS score (ranging from 0 to 14, whereby higher a scoring reflects greater adherence to the MedDiet) increased significantly from 6.53 ± 2 to 7.34 ± 1.93 during the confinement. Multivariate logistic regression models, adjusted for age, gender, region and other variables, showed a statistically significant higher likelihood of changing the adherence to the MedDiet (towards an increase in adherence) in those persons who decreased the intake of fried foods, snacks, fast foods, red meat, pastries or sweet beverages, but increased MedDiet-related foods such as olive oil, vegetables, fruits or legumes during the confinement. COVID-19 confinement in Spain has led to the adoption of healthier dietary habits/behaviours in the studied population, as reflected by a higher adherence to the MedDiet. This improvement, if sustained in the long-term, could have a positive impact on the prevention of chronic diseases and COVID-19-related complications.
The European Prospective Investigation into Cancer and Nutrition (EPIC) is a multicentre prospective study conducted in 23 centres in 10 European countries. Here we review the findings from EPIC on ...the relationship between diet-related exposures and incidence or mortality from the four most frequent cancers in the European population: colorectal, breast, lung, and prostate cancer. We conducted a systematic review following PRISMA guidelines and identified 110 high-quality studies based on the EPIC cohort. Fruit and vegetable consumption had a protective effect against colorectal, breast, and lung cancer, whereas only fruit had a protective effect against prostate cancer. A higher consumption of fish and lower consumption of red and processed meat were related with a lower risk of colorectal cancer; and higher consumption of fatty fish with lower risk of breast cancer. Calcium and yogurt intake were found to protect against colorectal and prostate cancer. Alcohol consumption increased the risk for colorectal and breast cancer. Finally, adherence to the Mediterranean diet emerged as a protective factor for colorectal and breast cancer. The EPIC study results are in agreement with the latest evidence from leading authorities on cancer prevention and help to inform public prevention policies and strategies.
To identify gut and oral metagenomic signatures that accurately predict pancreatic ductal carcinoma (PDAC) and to validate these signatures in independent cohorts.
We conducted a multinational study ...and performed shotgun metagenomic analysis of fecal and salivary samples collected from patients with treatment-naïve PDAC and non-PDAC controls in Japan, Spain, and Germany. Taxonomic and functional profiles of the microbiomes were characterized, and metagenomic classifiers to predict PDAC were constructed and validated in external datasets.
Comparative metagenomics revealed dysbiosis of both the gut and oral microbiomes and identified 30 gut and 18 oral species significantly associated with PDAC in the Japanese cohort. These microbial signatures achieved high area under the curve values of 0.78 to 0.82. The prediction model trained on the Japanese gut microbiome also had high predictive ability in Spanish and German cohorts, with respective area under the curve values of 0.74 and 0.83, validating its high confidence and versatility for PDAC prediction. Significant enrichments of Streptococcus and Veillonella spp and a depletion of Faecalibacterium prausnitzii were common gut signatures for PDAC in all the 3 cohorts. Prospective follow-up data revealed that patients with certain gut and oral microbial species were at higher risk of PDAC-related mortality. Finally, 58 bacteriophages that could infect microbial species consistently enriched in patients with PDAC across the 3 countries were identified.
Metagenomics targeting the gut and oral microbiomes can provide a powerful source of biomarkers for identifying individuals with PDAC and their prognoses. The identification of shared gut microbial signatures for PDAC in Asian and European cohorts indicates the presence of robust and global gut microbial biomarkers.
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This study analyzed the gut and oral microbiomes of patients with pancreatic cancer and showed the potential of the microbial species to be used as a biomarker for the disease and its prognosis.
Long-term cancer survivors represent a sizeable portion of the population. Plant-based foods may enhance the prevention of cancer-related outcomes in these patients. We aimed to synthesize the ...current evidence regarding the impact of plant-based dietary patterns (PBDPs) on cancer-related outcomes in the general population and in cancer survivors. Considered outcomes included overall cancer mortality, cancer-specific mortality, and cancer recurrence. A rapid review was conducted, whereby 2234 original articles related to the topic were identified via Pubmed/Medline. We selected 26 articles, which were classified into studies on PBDPs and cancer outcomes at pre-diagnosis: vegan/vegetarian diet (
= 5), provegetarian diet (
= 2), Mediterranean diet (
= 13), and studies considering the same at post-diagnosis (
= 6). Pooled estimates of the associations between the aforementioned PBDPs and the different cancer outcomes were obtained by applying random effects meta-analysis. The few studies available on the vegetarian diet failed to support its prevention potential against overall cancer mortality when compared with a non-vegetarian diet (e.g., pooled hazard ratio (HR) = 0.97; 95% confidence interval (CI): 0.88-1.06). The insufficient number of studies evaluating provegetarian index scores in relation to cancer mortality did not permit a comprehensive assessment of this association. The association between adherence to the Mediterranean diet and cancer mortality reached statistical significance (e.g., pooled HR = 0.84; 95% CI: 0.79-0.89). However, no study considered the influence of prognostic factors on the associations. In contrast, post-diagnostic studies accounted for prognostic factors when assessing the chemoprevention potential of PBDPs, but also were inconclusive due to the limited number of studies on well-defined plant-based diets. Thus, whether plant-based diets before or after a cancer diagnosis prevent negative cancer-related outcomes needs to be researched further, in order to define dietary guidelines for cancer survivors.
diet quality indexes are tools are aimed at quantifying the compliance to a defined dietary pattern. These indexes are a combined measure of dietary factors (food groups, foods, nutrients and ratios) ...and/ or lifestyles factors. The Mediterranean Diet (MD) is a dietary pattern characterized by their positive effects against chronic diseases. There have been many indexes proposed for the assessment of this dietary pattern. An evaluation of their composition and health benefits is therefore convenient.
the objective is to evaluate indexes of adherence to the MD with regard to their definition, methodological issues and validation as reported in epidemiological studies.
we searched in PubMed for studies that developed MD Indexes up to October 2014.
a total number of 22 indexes were identified, with differences regarding the number of components (7-28), scoring (0, 1, 2, 3, 4, 5, 8 or 10, in case of compliance), range (0-100) and type of components (which could be food groups/foods or their combination, with nutrients). Among the positive components, fruits and vegetables were the most common and meats, among the negative components. There were also differences with regard to their composition and evaluation (e.g. criteria of moderate alcohol consumption), as well as with the scoring system (in medians, terciles or established servings).
this review suggests that since there is great heterogeneity in the definition of MD. It would be therefore convenient to establish more clearly the components to be included and to establish commonly defined criteria to quantify this dietary pattern.
The current epidemiologic evidence suggests that men with type 2 diabetes mellitus may be at lower risk of developing prostate cancer, but little is known about its association with stage and grade ...of the disease. The association between self‐reported diabetes mellitus at recruitment and risk of prostate cancer was examined in the European Prospective Investigation into Cancer and Nutrition (EPIC). Among 139,131 eligible men, 4,531 were diagnosed with prostate cancer over an average follow‐up of 12 years. Multivariable hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models stratified by EPIC‐participating center and age at recruitment, and adjusted for education, smoking status, body mass index, waist circumference, and physical activity. In a subset of men without prostate cancer, the cross‐sectional association between circulating concentrations of androgens and insulin‐like growth factor proteins with diabetes status was also investigated using linear regression models. Compared to men with no diabetes, men with diabetes had a 26% lower risk of prostate cancer (HR, 0.74; 95% CI, 0.63–0.86). There was no evidence that the association differed by stage (p‐heterogeneity, 0.19) or grade (p‐heterogeneity, 0.48) of the disease, although the numbers were small in some disease subgroups. In a subset of 626 men with hormone measurements, circulating concentrations of androstenedione, total testosterone and insulin‐like growth factor binding protein‐three were lower in men with diabetes compared to men without diabetes. This large European study has confirmed an inverse association between self‐reported diabetes mellitus and subsequent risk of prostate cancer.
What's new?
Emerging evidence suggests that men with type 2 diabetes are at lower risk to develop prostate cancer. Using data obtained within the European Prospective Investigation into Cancer and Nutrition (EPIC), the authors show that the prostate cancer risk was, indeed, reduced by 26% in men with type 2 diabetes but no association with cancer stage or grade was observed. In a subset of men for whom data on circulating hormones were available, levels of androstenedione, total testosterone and insulin‐like growth factor binding protein‐three were lower in those with diabetes as compared to those without diabetes, giving clues to how having diabetes could affect prostate cancer development.
Inverse associations of coffee and/or tea in relation to hepatocellular carcinoma (HCC) risk have been consistently identified in studies conducted mostly in Asia where consumption patterns of such ...beverages differ from Europe. In the European Prospective Investigation into Cancer and nutrition (EPIC), we identified 201 HCC cases among 486,799 men/women, after a median follow‐up of 11 years. We calculated adjusted hazard ratios (HRs) for HCC incidence in relation to quintiles/categories of coffee/tea intakes. We found that increased coffee and tea intakes were consistently associated with lower HCC risk. The inverse associations were substantial, monotonic and statistically significant. Coffee consumers in the highest compared to the lowest quintile had lower HCC risk by 72% HR: 0.28; 95% confidence intervals (CIs): 0.16–0.50, p‐trend < 0.001. The corresponding association of tea with HCC risk was 0.41 (95% CI: 0.22–0.78, p‐trend = 0.003). There was no compelling evidence of heterogeneity of these associations across strata of important HCC risk factors, including hepatitis B or hepatitis C status (available in a nested case–control study). The inverse, monotonic associations of coffee intake with HCC were apparent for caffeinated (p‐trend = 0.009), but not decaffeinated (p‐trend = 0.45) coffee for which, however, data were available for a fraction of subjects. Results from this multicentre, European cohort study strengthen the existing evidence regarding the inverse association between coffee/tea and HCC risk. Given the apparent lack of heterogeneity of these associations by HCC risk factors and that coffee/tea are universal exposures, our results could have important implications for high HCC risk subjects.
What's new?
Could coffee and tea consumption protect from liver cancer? The answer is yes! In this first multi‐center European cohort study, intake of coffee and, to a lesser extent, tea was associated, in a dose‐dependent manner, with lower risk of hepatocellular carcinoma. For the most loyal coffee consumers, risk was reduced by 72%. No protection was observed with decaffeinated coffee. As caffeinated coffee and tea are almost universal exposures, these results may have important implications for individuals at high risk for liver cancer.
Objective
The aim of this study was to evaluate the associations among the intake of total polyphenols, polyphenol classes, and polyphenol subclasses and body weight change over 5 years.
Methods
A ...total of 349,165 men and women aged 25 to 70 years were recruited in the Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home and Obesity (PANACEA) project of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort from nine European countries. Body weight was measured at baseline and at follow‐up after a median time of 5 years. Polyphenol intake, including four main polyphenol classes and eighteen subclasses, was estimated using validated dietary questionnaires and Phenol‐Explorer. Multilevel mixed linear regression models were used to estimate the associations.
Results
Participants gained, on average, 2.6 kg (±5.0 kg) over 5 years. Total flavonoids intake was inversely associated with body weight change (−0.195 kg/5 years, 95% CI: −0.262 to −0.128). However, the intake of total polyphenols (0.205 kg/5 years, 95% CI: 0.138 to 0.272) and intake of hydroxycinnamic acids (0.324 kg/5 years, 95% CI: 0.267 to 0.381) were positively associated with body weight gain. In analyses stratified by coffee consumption, hydroxycinnamic acid intake was positively associated with body weight gain in coffee consumers (0.379 kg/5 years, 95% CI: 0.319 to 0.440), but not in coffee nonconsumers (−0.179 kg/5 years, 95% CI: −0.490 to 0.133).
Conclusions
Higher intakes of flavonoids and their subclasses are inversely associated with a modest body weight change. Results regarding hydroxycinnamic acids in coffee consumers require further investigation.
Oxidative Balance Scores (OBSs) are tools that have emerged to evaluate the global balance of individuals' oxidation-reduction status. The aim was to compare OBSs available in the literature ...regarding their characteristics and associations with chronic diseases in epidemiological studies. Studies that developed OBSs were searched in PubMed until August 2018. A total of 21 OBSs were identified. These OBSs presented different scoring schemes and different types of anti- and pro-oxidant components, including dietary factors (dietary intake and/or nutrient biomarkers), lifestyle factors, and medications. Most OBSs were based on over 10 components, and some included only dietary factors. Few considered weighted components in the score. Only three OBSs were validated as potential surrogates of oxidative balance through inflammation and OS-related biomarkers. Notably, all the OBSs were associated-to a varying degree-with a reduced risk of cardiovascular diseases, chronic kidney disease, colorectal adenomas, and different cancer types (colorectal and breast cancer), as well as with all-cause and cancer-related mortality. For other outcomes, e.g., prostate cancer, contradictory results were reported. In summary, there is a great heterogeneity in the definition of OBSs. Most studies are concordant in supporting that excessive OS reflected by a lower OBS has deleterious effects on health. Unified criteria for defining the proper OBSs, valuable to gauge OS-related aspects of the diet and lifestyle that may lead to adverse health outcomes, are needed.
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