Instituto de Salud Pública de Navarra

Polyphenols represent the largest and most diverse class of dietary antioxidants. Epidemiological evidence linking specific (poly)phenol classes, such as flavonoids and lignans, to breast cancer (BC) risk remains limited and largely inconclusive in prospective studies. The aim of this study is to examine the association between the intake of total (poly)phenols-and its classes and subclasses-and BC risk-overall and by subtypes (estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2))-in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The EPIC cohort includes 257,960 adult women from seven European countries. During a mean follow-up of 14 years, there were 10,722 incident overall BC cases. Associations were computed using Cox regression models adjusted for potential confounders. No significant associations were found between total (poly)phenol intake and overall BC risk (HRQ5 vs. Q1 = 1.02; 95% CI: 0.95-1.11). In addition, null associations were mostly found between classes and subclasses of (poly)phenols and BC subtypes. After stratifying by menopausal status, no significant associations were observed. In conclusion, this study found no evidence of associations between the intake of any class or subclass of (poly)phenols and BC risk in the European population.

Pleural mesothelioma (PM) is a rare, asbestos-linked cancer with a long asymptomatic latency, delaying diagnosis and limiting treatment options. Identifying blood‐based biomarkers that signal disease before symptoms onset could improve surveillance of at‐risk individuals. In our work, we conducted a prospective proteomic study of pre-diagnostic serum from 21 PM cases (< 5 years before diagnosis) and 21 asbestos‐exposed controls in the EPIC cohort using SWATH‐MS, followed by ELISA validation. Findings were tested in an independent MoMar cohort of 32 pre‐diagnostic plasma samples (< 1 year before diagnosis) and 32 matched controls. SWATH-MS identified 12 differentially expressed proteins (nominal p < 0.05, fold change > 1.3 or < 0.75). Transferrin and complement C4A were elevated, while beta‐2‐microglobulin and dermcidin were reduced in pre‐diagnostic cases. ELISA confirmed a borderline significant rise in beta‐2‐microglobulin within two years of diagnosis in EPIC. Calretinin and mesothelin were also detected in both cohorts, with the five‐marker panel achieving an AUC of 0.91 (p = 0.001) in MoMar but not reaching significance in EPIC (AUC = 0.88, p = 0.17). Integrating novel proteomic biomarker candidates with established markers enhances early PM detection in high-risk populations. Larger, multi‐cohort validation is warranted to refine this biomarker panel for clinical surveillance.

Pleural mesothelioma (PM) is a lethal cancer primarily caused by asbestos exposure. Not all exposed individuals develop PM, suggesting the involvement of additional factors. This underscores the need for robust predictive models integrating biomarkers from multi-omic domains to improve risk stratification and early detection. We developed and evaluated polygenic risk scores (PRS) and methylation risk scores (MRS) using a retrospective case-control study (749 participants: 387 PM cases, 362 controls) and a nested case-control European Prospective Investigation into Cancer and Nutrition (EPIC)-Meso study (268 participants: 134 preclinical PM cases, 134 matched controls) within the EPIC cohort. Genome-wide association analyses in the retrospective case-control study identified PM-associated variants. The PRS (1123 SNPs with p < 0.001) in the retrospective training subset stratified disease risk in the test set (ORs 3.46-9.54 across top percentiles) and improved model discrimination (AUC = 0.75 vs. 0.71 in baseline model, p = 0.04). In EPIC-Meso, PRS performance was limited (AUC = 0.52). External validation in the UK-Biobank (UKBB) confirmed a modest but consistent association with PM-risk. A Meta-PRS derived from the UKBB-FinnGen meta-analysis replicated this trend in the full retrospective dataset, showing higher OR across top percentiles (2.5-12.3) and improved discrimination (AUC 0.74 vs. 0.72, p = 0.016). MRS, with 68 differentially methylated CpGs (effect-size >|0.10|, FDR p < 0.05) in the retrospective training set, increased the AUC from 0.66 to 0.85 (p < 0.001) in the test set and from 0.51 to 0.62 in EPIC-Meso. PRS was most predictive in low-exposure groups, while MRS remained robust across exposure levels. Combined PRS-MRS models improved discrimination. Integrating multi-omic biomarkers can enhance PM-risk stratification and support earlier, targeted interventions in high-risk asbestos-exposed groups.

BackgroundProcessed meat (PM) consumption is an established risk factor for colorectal cancer (CRC). It has been hypothesized that nitrosyl-heme, formed by the addition of nitrites during meat processing, may enhance the carcinogenic effects of PMs. This study aims to investigate the association between nitrosyl-heme intake and CRC risk within the European Prospective Investigation into Cancer and Nutrition(EPIC) study.MethodsThis prospective study included 367,463 participants(70.3% women) from seven countries from the EPIC-study. Dietary data were collected via baseline questionnaires, and nitrosyl-heme exposure was estimated using biochemical data from 52 Spanish PMs, extrapolated to country-specific items. Sex-specific multivariable-adjusted hazard ratios(HRs) and 95% confidence intervals(CIs) were calculated using Cox proportional hazards models.ResultsOver a 15-year median follow-up, 5,115 incident CRC cases were identified. Comparing the highest vs. the lowest sex-specific tertile of nitrosyl-heme intake we found no significant association with CRC risk (HRT3vsT1:1.01;95%CI:0.93–1.09). Subgroup analyses by tumor subtype and interactions with lifestyle factors also showed no associations.ConclusionsThis study offers insights into nitrosyl-heme exposure in European populations but found no link to CRC risk. Further research is needed to understand nitrosyl-heme's role in CRC.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12937-025-01266-7.

BackgroundAlcohol consumption has been described to exhibit a J-shaped relationship with dementia risk, but previous observations may be partly biased due to “sick-quitters” and competing risks of death.ObjectiveTo examine the association between baseline and lifetime alcohol consumption and the risk of dementia and subtypes in a large Mediterranean cohort, accounting for lifetime drinking patterns, potential confounding, and competing risks of death.MethodsProspective study of 30,211 participants, 29–69 years at recruitment (1992–1996), from the EPIC-Spain dementia cohort. Alcohol intake was assessed using a validated dietary history and retrospective questionnaires covering ages 20, 30, and 40 years. Dementia cases (n = 1,114) were ascertained through linkage with healthcare and mortality databases and individual medical record review over a mean follow-up of 22.8 years. Multivariate competing risk models were used to estimate sub-hazard ratios (sHRs) for dementia by categories of baseline and lifetime alcohol consumption, using lifetime abstainers as the reference group.ResultsMean lifetime alcohol consumption was 41.9 and 4.4 g/d in men and women, respectively. No significant associations were found between baseline or lifetime alcohol consumption and risk of overall dementia (sHRcurrentvs.never = 0.96, 95% CI: 0.82, 1.13; sHRevervs.never = 0.96, 95% CI: 0.82, 1.11), Alzheimer's disease, or non-Alzheimer subtypes. These null findings remained consistent across strata of sex, BMI or smoking categories, and by beverage type. Sensitivity analyses excluding mis-reporters of energy intake or low-quality diagnoses yielded similar results.ConclusionsIn this large prospective cohort with over 1,100 dementia cases and long-term follow-up, alcohol consumption was not significantly associated with dementia risk. These findings challenge the notion of a protective effect of moderate drinking and warrant continued investigation using methodologically rigorous approaches to clarify the role of alcohol dose, timing, and pattern on dementia risk.