Search Results (4)

Background: Colorectal cancer (CRC) is characterized by the uncontrolled growth of malignant colonic or rectal crypt epithelium. About 85% of CRCs evolve through a stepwise progression from advanced precancerous adenoma lesions. A better understanding of the evolution from adenoma to carcinoma can provide a window of opportunity not only for early detection and therapeutic intervention but potentially also for cancer prevention strategies. Methods: This study investigates the heterogeneous methylation, copy-number alteration (CNA), and mutation signals of histological adenoma subtypes in the context of progression from normal colon to advanced precancerous lesions (APLs) and early-stage CRC. Results: Differential methylation analysis revealed 2321 significantly altered regions among APLs: 137 hypermethylated regions in serrated vs. tubular, 2093 in serrated vs. tubulovillous, and 91 in tubular vs. tubulovillous adenoma subtypes. The most differentiating pathways for serrated adenomas belonged to cAMP signaling and the regulation of pluripotency of stem cells, while regions separating tubular and tubulovillous subtypes were enriched for WNT signaling. CNA events were mostly present in tubular or tubulovillous adenomas, with the most frequent signals being seen in chromosomes 7, 12, 19, and 20. In contrast, early-stage CRC exhibited signals in chromosomes 7, 8, and 20, indicating different processes between APL and early-stage CRC. Mutations reinforce subtype-level differences, showing specific alterations in each subtype. Conclusions: These findings are especially important for developing early detection or cancer prevention tests trying to capture adenoma signatures. Full article

Atherosclerotic cardiovascular disease remains a major health issue, often developing silently as subclinical atherosclerotic disease (SAD). The Mediterranean diet (MDiet) is known for its cardiovascular benefits, but the combined influence of both MDiet adherence and physical activity (PA) on SAD progression has not been previously documented. Objective: We aimed to investigate how adherence to a healthy lifestyle, defined as MDiet adherence and PA level, influences SAD progression in subjects from the ILERVAS cohort follow-up. Methods: A study on 3097 participants from the ILERVAS prospective cohort was conducted. MDiet adherence was assessed using the MEDAS score, and PA categories were established using the IPAQ, both categorized into low, moderate, and high levels. Two different lifestyle scores integrating the MDiet and PA categories were built. The presence of atherosclerotic plaques was assessed by carotid and femoral ultrasound examination. Demographic, clinical, and biochemical data were also obtained. Multivariable linear, logistic, and Poisson regression models adjusted for potential confounders were used to analyze the association between the lifestyle scores and SAD progression, as well as the MDiet and PA as separate variables and number of territories with plaque. Results: A healthier lifestyle score did not show an effect on SAD progression. However, a higher MEDAS score was associated with a 3% decrease in the number of territories with plaque (IRR 0.97, 95% CI 0.96–0.99, p < 0.001), suggesting a protective effect of the adherence to the MDiet. PA did not show a significant association (IRR 1.00, 95% CI 1.00–1.00, p = 0.269). Older age, hypertension, dyslipidemia, smoking, and lower eGFR were associated with SAD progression, while the female sex was protective (IRR 0.67, 95% CI 0.63–0.72, p < 0.001). Conclusions: The findings of this study show that higher adherence to the MDiet is associated with reduced incidence of SAD, indicating its potential role in cardiovascular prevention strategies. Although a higher lifestyle score or physical activity levels did not show any significant effect, promoting the MDiet, alongside managing traditional cardiovascular risk factors, could be an effective public health intervention to prevent atherosclerosis and reduce the burden of cardiovascular disease. Full article

The use of non-invasive liquid biopsy-based cell-free DNA (cfDNA) analysis is an emerging method of cancer detection and intervention. Different analytical methodologies are used to investigate cfDNA characteristics, resulting in costly and long analysis processes needed for combining different data. This study investigates the possibility of using cfDNA data converted for methylation analysis for combining the cfDNA fragment size with copy number variation (CNV) in the context of early colorectal cancer detection. Specifically, we focused on comparing enzymatically and bisulfite-converted data for evaluating cfDNA fragments belonging to chromosome 18. Chromosome 18 is often reported to be deleted in colorectal cancer. We used counts of short and medium cfDNA fragments of chromosome 18 and trained a linear model (LDA) on a set of 2959 regions to predict early-stage (I–IIA) colorectal cancer on an independent test set. In total, 87.5% sensitivity and 92% specificity were obtained on the enzymatically converted libraries. Repeating the same workflow on bisulfite-converted data yielded lower accuracy results with 58.3% sensitivity, implying that enzymatic conversion preserves the cancer fragmentation footprint in whole genome data better than bisulfite conversion. These results could serve as a promising new avenue for the early detection of colorectal cancer using fragmentation and methylation approaches on the same datasets. Full article