Lisa Padroni

Circulating microRNAs (miRNAs) are promising minimally invasive biomarkers for cancer risk assessment, yet prospective evidence for breast cancer (BC) remains limited. We conducted a nested case–control study within a prospective cohort to examine whether pre-diagnostic circulating miRNAs are associated with subsequent BC risk and to explore their potential relevance in prospective population-based settings. Baseline serum from 160 women (80 incident BC cases; 80 matched controls) was analyzed, with a median time to diagnosis of 8.9 years. Eight candidate miRNAs were quantified by droplet digital PCR (ddPCR) and normalized to miR-484. Group differences were evaluated by non-parametric tests, and odds ratios for BC were estimated using logistic regression models adjusted for established risk factors, with Bonferroni correction for multiple testing. Cases and controls were comparable at baseline. Among the candidates, lower circulating miR-181 levels showed a suggestive inverse association with BC risk in fully adjusted models, while lower Let7 levels showed only a non-significant, hypothesis-generating inverse trend that did not survive Bonferroni correction. No other miRNA displayed clear associations with BC risk. These findings, while preliminary, support further large-scale prospective investigations specifically designed to assess predictive performance and external validation. employing standardized pre-analytical and analytical protocols, repeated sampling, and independent replication/external validation to clarify the etiologic relevance and potential risk-prediction value of circulating miRNAs for BC.

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 (HR_{Q5 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.

Circulating microRNAs (miRNAs) have emerged as non-invasive biomarkers that may be associated with cancer risk, but their role in the development of colon cancer is still not well understood. We conducted a nested case-control study within the EPIC-Italy cohort to investigate the association between pre-diagnostic serum levels of eight candidate miRNAs (Let7, Mir21, Mir155, Mir181, Mir222, Mir145, Mir92, and Mir20) and subsequent colon cancer occurrence. A total of 104 incident colon cancer cases were matched to 104 controls by center, sex, age, recruitment date, and vital status. miRNA expression was quantified using RT-qPCR and normalized to Mir484. Logistic regression models were applied to estimate odds ratios, 95% confidence intervals, and p-values, adjusting for age at recruitment, smoking status, body mass index, physical activity, adherence to a Mediterranean diet, and socioeconomic position. Elevated expression of Let7 (OR = 0.91; 95% CI: 0.84–1.00; p = 0.04) was associated with slightly lower odds of colon cancer in unadjusted models. Mir21 and Mir222 showed borderline associations (p = 0.07 and p = 0.09, respectively), but these did not remain significant after Bonferroni correction. This result was consistent in the multivariate logistic model: higher levels of Let7 (OR = 0.91; 95% CI: 0.82–1.00; p = 0.06) and Mir222 (OR = 0.75; 95% CI: 0.57–1.00; p = 0.05) are suggestive of an association with lower odds of colon cancer. Our findings highlight the challenges of using circulating miRNAs as very early biomarkers, particularly when samples are collected nearly a decade before diagnosis. Future studies with larger sample sizes, serial blood collections, and integration with inflammatory and immune markers will be crucial to clarify the temporal dynamics of circulating miRNA alterations and their potential role in risk-adapted screening strategies.

Background/Objectives: Endometrial cancer (EC)’s major risk factors include obesity and diabetes, both strongly related with lifestyle choices and dietary factors. Our study aimed to evaluate the relationship between diabetes-related dietary patterns, EC risk, and survival in a population of middle-aged European women. Methods: A total of 285,418 female participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study were included in the analysis. After a mean time of 10.6 years of follow-up, 1955 incident EC cases were registered; of those, 133 women died from EC. The Empirical Dietary Index for Insulin Resistance (EDIR), the Empirical Dietary Index for Hyperinsulinemia (EDIH), and the Diabetes Risk Reduction Diet (DRRD), were estimated from dietary information collected at baseline from EPIC participants. Cox proportional hazards regression models were used to evaluate the association between the dietary patterns and EC risk, using hazard ratios (HR), 95% confidence intervals (CI), and adjusting for relevant confounders. Cox and Fine–Gray models were used to assess the association with overall and EC-specific mortality, respectively. Results: Higher adherence to EDIR was associated with an increased risk of EC, multivariable HR for T3vsT1 were 1.17 (95% CI = 1.04 to1.31). However, when BMI was included in the models, these associations became weaker and no longer statistically significant. No associations were observed in relation to adherence to EDIH, DRRD, and EC risk. No associations were found in relation to diabetes-related dietary patterns and mortality. Conclusions: This study highlights the potential role of diabetes related dietary patterns and EC etiology and prevention. Further studies are warranted to better understand the role of etiology-derived dietary patterns and disease prevention and prognosis.

Mycotoxins have been hypothesized to contribute to a diversity of adverse health effects in humans, even at low concentrations. Certain mycotoxins are established human carcinogens, whereas for others research suggests potential carcinogenic effects. The aim of this study was to determine the association between dietary exposure to mycotoxins and hepatobiliary cancers in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. EPIC questionnaire data were matched to mycotoxin food occurrence data compiled by the European Food Safety Authority to assess long-term dietary mycotoxin exposure (expressed as μg/kg body weight/day) and then relate them to the risk of hepatocellular carcinoma (HCC) (n = 255) and biliary tract cancers (n = 273). Analyses were conducted using multivariable Cox proportional hazards regression models to compute hazard ratios (HR) and 95% confidence intervals (95% CI). Key food groups contributing to mycotoxin exposure were cereals and cereal-based products, vegetables, non-alcoholic beverages (including fruit juices) and fruits. Estimated intake of deoxynivalenol (DON) and its derivatives was positively associated with HCC risk (HR_T3vsT1: 1.90, 95% CI: 1.18–3.05, p-trend <0.01). No statistically significant associations were found for the other mycotoxins. Further research to confirm our observations and investigate potential underlying mechanisms of these compounds is warranted. These data may provide evidence of HCC risks associated with higher dietary intake levels of DON, which has not yet been classified as a human carcinogen.

Background/Objectives: Charlson Comorbidity Index (CCI) is one of the most reliable indicators to assess the impact of multimorbidity on COVID-19-related outcomes. Moreover, the patient’s clinical conditions are associated with SARS-CoV-2 outcomes. This study aimed to analyze the association between multimorbidity and COVID-19-related outcomes, evaluating whether the National Early Warning Score 2 (NEWS2) mediated these associations. Methods: Data were obtained through the platform “EPICLIN”. We analyzed all patients who tested positive for COVID-19 after accessing the emergency department (ED) of San Luigi Gonzaga (Orbassano) and Molinette (Turin) hospitals from 1 March to 30 June 2020. Different outcomes were assessed: non-discharge from the ED, 30-day mortality, ICU admission/death among hospitalized patients, and length of hospitalization among surviving patients. Two subgroups of patients (<65 and 65+ years old) were analyzed using logistic regressions, Cox models, and mediation analyses. Results: There was a greater risk of not being discharged or dying among those who were younger and with CCI ≥ 2. Moreover, the higher the CCI, the longer the length of hospitalization. Considering older subjects, a greater CCI was associated with a higher risk of death. Regarding the mediation analyses, multimorbidity significantly impacted the hospitalization length and not being discharged in the younger population. Instead, in the older population, the NEWS2 played a mediation role. Conclusions: This research showed that multimorbidity is a risk factor for a worse prognosis of COVID-19. Moreover, there was a strong direct effect of CCI on not being discharged, and the NEWS2 was found to act as mediator in the association between multimorbidity and COVID-19-related outcomes.