Early-onset colorectal cancer as an emerging disease of metabolic dysregulation.

Colorectal cancer (CRC) is one of the most common malignancies and the second leading cause of cancer-related death worldwide. Early-onset CRC (EOCRC), diagnosed in adults under the age of 50 years, has emerged as a pressing public health concern owing to its alarming rise in incidence since the 1990s. This trend, observed in the USA and at least eight other high-income countries, starkly contrasts with the declining incidence rates of late-onset CRC (age 50 years and above), largely attributed to early disease detection and lifestyle changes.

Pathway polygenic risk scores (pPRS) for the analysis of gene-environment interaction.

A polygenic risk score (PRS) is used to quantify the combined disease risk of many genetic variants. For complex human traits there is interest in determining whether the PRS modifies, i.e.

Red meat intake interacts with a TGF-β-pathway-based polygenic risk score to impact colorectal cancer risk: Application of a novel approach for polygenic risk score construction.

Background: High intake of red and/or processed meat are established colorectal cancer (CRC) risk factors. Genome-wide association studies (GWAS) have reported 204 variants (G) associated with CRC risk. We used functional annotation data to identify subsets of variants within known pathways and constructed pathway-based Polygenic Risk Scores (pPRS) to model pPRS x environment (E) interactions.

Relationship between magnesium intake and decline in kidney function, incident chronic kidney disease and incident cardiovascular disease.

Background And Hypothesis: Higher magnesium (Mg) intake is associated with a lower risk of stroke, heart failure and mortality, while there are limited data with kidney disease outcomes. We hypothesized that higher dietary Mg intake would be associated with a lower incidence of cardiovascular disease (CVD), chronic kidney disease (CKD) and kidney function decline.

Methods: The Health, Aging, and Body Composition Study is an observational cohort of 3075 community-dwelling older adults.

"PIK"ing the Right Patients for Adjuvant Aspirin Therapy for Colorectal Cancer.

Observational studies demonstrate that aspirin use after diagnosis of colorectal cancer, particularly tumors with mutated PIK3CA, improves outcomes. However, randomized controlled trial data are lacking. In this issue, we discuss the SAKK 41/13 adjuvant aspirin randomized controlled trial results in context of other adjuvant aspirin trials and emerging data on potential mechanisms of action.

Waist Circumference, a Body Shape Index, and Molecular Subtypes of Colorectal Cancer: A Pooled Analysis of Four Cohort Studies.

Background: Waist circumference (WC) and its allometric counterpart, "a body shape index" (ABSI), are risk factors for colorectal cancer; however, it is uncertain whether associations with these body measurements are limited to specific molecular subtypes of the disease.

Methods: Data from 2,772 colorectal cancer cases and 3,521 controls were pooled from four cohort studies within the Genetics and Epidemiology of Colorectal Cancer Consortium. Four molecular markers (BRAF mutation, KRAS mutation, CpG island methylator phenotype, and microsatellite instability) were analyzed individually and in combination (Jass types).

Pathway Polygenic Risk Scores (pPRS) for the Analysis of Gene-environment Interaction.

A polygenic risk score (PRS) is used to quantify the combined disease risk of many genetic variants. For complex human traits there is interest in determining whether the PRS modifies, i.e.

Novel metabolomic predictors of incident colorectal cancer in men and women.

Background: Metabolomic profiles may influence colorectal cancer (CRC) development. Few studies have performed prediagnostic metabolome-wide analyses with CRC risk.

Methods: We conducted a nested case-control study among women (Nurses' Health Study) and men (Health Professionals Follow-Up Study) who provided blood between 1989 and 1995.

Aspirin Use and Incidence of Colorectal Cancer According to Lifestyle Risk.

Importance: Aspirin reduces the risk of colorectal cancer (CRC). Identifying individuals more likely to benefit from regular aspirin use for CRC prevention is a high priority.

Objective: To assess whether aspirin use is associated with the risk of CRC across different lifestyle risk factors.

Community Collaboration to Advance Racial/Ethnic Equity in Colorectal Cancer Screening: Protocol for a Multilevel Intervention to Improve Screening and Follow-up in Community Health Centers.

Introduction: Colorectal cancer (CRC) screening utilization is low among low-income, uninsured, and minority populations that receive care in community health centers (CHCs). There is a need for evidence-based interventions to increase screening and follow-up care in these settings.

Methods: A multilevel, multi-component pragmatic cluster randomized controlled trial is being conducted at 8 CHCs in two metropolitan areas (Boston and Los Angeles), with two arms: (1) Mailed FIT outreach with text reminders, and (2) Mailed FIT-DNA with patient support.

Ethical Implications of Artificial Intelligence in Gastroenterology: The Co-pilot or the Captain?

Though artificial intelligence (AI) is being widely implemented in gastroenterology (GI) and hepatology and has the potential to be paradigm shifting for clinical practice, its pitfalls must be considered along with its advantages. Currently, although the use of AI is limited in practice to supporting clinical judgment, medicine is rapidly heading toward a global environment where AI will be increasingly autonomous. Broader implementation of AI will require careful ethical considerations, specifically related to bias, privacy, and consent.

Optimizing single-cell RNA sequencing methods for human colon biopsies: droplet-based vs. picowell-based platforms.

Background & Aims: Single-cell RNA sequencing (scRNA) has empowered many insights into gastrointestinal microenvironments. However, profiling human biopsies using droplet-based scRNA (D-scRNA) is challenging since it requires immediate processing to minimize epithelial cell damage. In contrast, picowell-based (P-scRNA) platforms permit short-term frozen storage before sequencing.

Stool Protein Mass Spectrometry Identifies Biomarkers for Early Detection of Diffuse-type Gastric Cancer.

There is a high unmet need for early detection approaches for diffuse gastric cancer (DGC). We examined whether the stool proteome of mouse models of gastric cancer (GC) and individuals with hereditary diffuse gastric cancer (HDGC) have utility as biomarkers for early detection. Proteomic mass spectrometry of the stool of a genetically engineered mouse model driven by oncogenic KrasG12D and loss of p53 and Cdh1 in gastric parietal cells [known as Triple Conditional (TCON) mice] identified differentially abundant proteins compared with littermate controls.

Acute Kidney Injury Receiving Dialysis and Dialysis Care after Hospital Discharge.

The number of patients with AKI receiving outpatient hemodialysis (AKI-D) is increasing. At present, on the basis of limited data, approximately one third of patients with AKI-D who receive outpatient dialysis after hospital discharge survive and regain sufficient kidney function to discontinue dialysis. Data to inform dialysis management strategies that promote kidney function recovery and processes of care among patients with AKI-D receiving outpatient dialysis are lacking.

Changes in Cognitive Function After Kidney Transplantation: A Longitudinal Cohort Study.

Rationale & Objective: Kidney disease negatively affects cognition. We assessed the effect of kidney transplantation (KT) on different cognitive domains.

Study Design: Prospective cohort study.

SARS-CoV-2 infection elucidates unique features of pregnancy-specific immunity.

Pregnancy is a risk factor for increased severity of SARS-CoV-2 and other respiratory infections. The mechanisms underlying this risk have not been well-established, partly due to a limited understanding of how pregnancy shapes immune responses. To gain insight into the role of pregnancy in modulating immune responses at steady state and upon perturbation, we collected peripheral blood mononuclear cells (PBMC), plasma, and stool from 226 women, including 152 pregnant individuals (n = 96 with SARS-CoV-2 infection and n = 56 healthy controls) and 74 non-pregnant women (n = 55 with SARS-CoV-2 and n = 19 healthy controls).