Early warning and screening of colorectal adenoma (CRA) is important for colorectal cancer (CRC) prevention. This study aimed to construct a non-invasive prediction model to improve CRA screening efficacy.

This study incorporated three cohorts, comprising 9747 participants who underwent colonoscopy. In cohort 1, 683 participants were prospectively recruited with comprehensive lifestyle information and faecal samples. CRA-associated bacteria were identified through 16S rRNA sequencing and quantitative real-time PCR. CRA prediction models were established using lifestyle and gut microbiota information. Cohort 2 prospectively enrolled 1529 participants to validate the lifestyle-based model, while cohort 3 retrospectively analysed 7535 individuals to determine the recommended initial colonoscopy screening ages for different risk groups based on age-specific CRA incidence rates.

Multivariable logistic regression yielded a prediction model incorporating 14 variables, demonstrating robust discrimination (c-statistic=0.79, 95% CI 0.75, 0.82). Other machine learning approaches showed comparable performance (random forest: 0.78, 95% CI 0.73, 0.81; gradient boosting: 0.78, 95% CI 0.76, 0.83). The ages for starting colonoscopy screening were established at 42 years for the high-risk group vs 53 years for the low-risk group. The inclusion of Fusobacterium nucleatum and pks+ Escherichia  coli enhanced the model's performance (c-statistic=0.84-0.86).

Integrated mathematical modelling incorporating lifestyle parameters and gut microbial signatures provides an effective non-invasive strategy for CRA risk stratification, while the accompanying machine learning-assisted prediction application enables cost-effective, population-level screening implementation to optimise CRC prevention protocols.

Metabolic syndrome (MetS) is a combination of risk factors that contribute to the development of many of today's chronic diseases. Rates of MetS continue to increase and it is now considered a worldwide epidemic. As with many chronic diseases it may take years for symptoms and the effects of MetS to manifest into severe health problems. Therefore, early detection is paramount A recently proposed method for the early detection of MetS is the assessment of an individual's metabolic flexibility during exercise. Metabolic flexibility is defined as the ability of the body to switch between energy substrates, primarily fats and carbohydrates, to produce energy and meet metabolic demand. This provides an indication of mitochondrial health, the possible beginning point of early insulin resistance and the development of MetS.Although there is widespread use of exercise and expired gas analysis to determine metabolic flexibility, there is no consensus on the appropriate guidelines, protocol, or interpretation of the subsequent data. Studies have used a variety of different protocols involving maximal and submaximal tests with step protocols ranging from 2 to 10 min, differences in data averaging, analysis, and stoichiometric equations, as well as variations in nutritional status of participants, and mode of exercise. This has led to considerable variation in reported results. Although the use of exercise to determine metabolic flexibility and act as a possible marker of early mitochondrial dysfunction holds significant promise, more work is required to determine the optimal protocol for clinical and research purposes.

Arginine plays a critical role in colorectal cancer (CRC) progression. We find that arginine catabolism is reduced in the intestinal microbiota of patients with CRC but increased in tumor tissue. We further verify that Escherichia coli can consume arginine via the arginine succinyltransferase (AST) pathway, and gavaging mice with the AST-deficient E. coli Nissle 1917 (ΔacEcN) can inhibit arginine catabolism of the intestinal microbiota, thereby increasing the arginine concentration in the colon. In the azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CRC mouse model, reduced arginine catabolism in the intestinal microbiota increases the arginine concentration in the tumor microenvironment, thereby activating the nitric oxide (NO) synthesis pathway and polyamine synthesis pathway in tumor tissues, stimulating angiogenesis in the tumor microenvironment, inducing M2 macrophage polarization, and activating the Wingless/Integrated (Wnt)/β-catenin pathway, ultimately accelerating CRC progression. This study reveals that intestinal microbiota can affect CRC progression through arginine catabolism, providing a potential target for the prevention and therapy of CRC.

Fatty liver is characterized by hepatic steatosis and is associated with dyslipidemia and insulin resistance. Carotid atherosclerosis, characterized by plaque formation, may be related to increased lipid deposition. High-density lipoprotein cholesterol (HDL-C) plays a role in reverse cholesterol transport. Colorectal cancer (CRC) is significantly associated with lipid metabolism-related diseases. However, there is a paucity of research on the relationship between lipid metabolism disorders and CRC.

To determine whether fatty liver (F), carotid atherosclerosis (A), and HDL-C (H) models (FAH) have predictive value for the occurrence of CRC and can be used for CRC screening.

A case-control study was conducted on 166 patients with CRC and 448 patients who underwent physical examinations at Ziyang People's Hospital between September 2018 and August 2023. A 1:3 individual matching strategy was used to establish the independent risk factors for CRC using univariate and multivariate analyses. A model was constructed based on independent risk factors, and its accuracy and sensitivity were verified. The discriminative ability, calibration, and clinical utility of the predictive model were evaluated using the Receiver Operating Characteristic curve, bootstrap resampling method, the Hosmer-Lemeshow goodness-of-fit test, and Decision Curve Analysis (DCA).

Fatty liver (F), carotid atherosclerosis (A), HDL-C (H), and intestinal dysbiosis (D) were identified as independent risk factors for CRC. The odds ratios were 2.885, 11.452, 24.659, and 22.445, respectively, p < 0.001. Based on these results, an FAH prediction model was established. The Horser-Lemeshow test for the FAH prediction model yielded p = 0.710. The cut-off value was 0.275, with the area under the curve of 0.902 (95% Confidence Interval: 0.875-0.929), p < 0.001. The sensitivity was 86.7%, and the specificity was 78.1%. A nomogram was created, and the internal calibration chart showed that the calibration curve closely aligned with the standard curve, indicating good discrimination and predictive ability of the model. DCA demonstrated that the model had a favorable clinical net benefit.

The FAH model has predictive value for CRC occurrence owing to its noninvasive nature and easy availability of data, making it worthy of further clinical research.

Whether HCV infection is associated with colorectal cancer (CRC) development remains inconclusive.

A nationwide population-based cohort study of the Taiwan National Health Insurance Research Database was conducted.

From 2003 to 2012, 1:2:2 propensity score-matched HCV-treated [interferon-based therapy ≥ 6 months, surveys for CRC (n = 9017), colon cancer (CC) (n = 9,022) and rectal cancer (RC) (n = 9,033), HCV-untreated and HCV-uninfected cohorts CRC (n = 18034), CC (n = 18,044) and RC (n = 18,066) were enrolled. The HCV-uninfected cohort had the lowest cumulative incidence of CRC (0.117%; 95% CI: 0.062%-0.207%), whereas the HCV-treated (0.966%; 0.375-2.122%) and HCV-untreated (0.807%; 0.485%-1.280%) cohorts had similar incidences (P = .0662); HCV infection [reference: HCV-untreated cohort, HCV-treated: hazard ratio (HR): 0.598; 95% CI HR: 0.337-1.059; HCV-uninfected: 0.250; 0.138-0.456] and age ≥ 49 years (3.128;1.751-5.59) were associated with CRC development. The HCV-untreated cohort had the highest cumulative incidence of CC (0.883%; 0.371-1.839%), while HCV-treated (0.478%; 0.110-1.518%) and HCV-uninfected cohorts (0.147%; 0.071-0.284%) had similar incidences (P = .4853); HCV infection (HCV-treated: 0.474; 0.232-0.971; HCV-uninfected: 0.338; 0.184-0.62), male sex (2.18; 1.301-3.654), age≥ 49 years (4.818; 2.123-10.936) and diabetes (1.983; 1.205-3.262) were associated with CC development. A higher RC cumulative incidence was noted in the HCV-untreated cohort (0.332%; 0.151-0.664%) than in the HCV-uninfected cohort (0.116%; 0.054-0.232%) (P = .0352); HCV infection (HCV-treated: 0.691; 0.295-1.617; HCV-uninfected: 0.424; 0.207-0.867), age ≥ 49 years (3.745, 1.576-8.898) and stroke (3.162; 1.366-7.322) were associated with RC development.

The baseline associations were HCV infection and age ≥ 49 years with CRC; male sex and diabetes with CC; and stroke with RC. Anti-HCV therapy might reverse the risk of HCV-related CC but not RC.

The American Heart Association (AHA), in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, nutrition, sleep, and obesity) and health factors (cholesterol, blood pressure, glucose control, and metabolic syndrome) that contribute to cardiovascular health. The AHA Heart Disease and Stroke Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, brain health, complications of pregnancy, kidney disease, congenital heart disease, rhythm disorders, sudden cardiac arrest, subclinical atherosclerosis, coronary heart disease, cardiomyopathy, heart failure, valvular disease, venous thromboembolism, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs).

The AHA, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States and globally to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2025 AHA Statistical Update is the product of a full year's worth of effort in 2024 by dedicated volunteer clinicians and scientists, committed government professionals, and AHA staff members. This year's edition includes a continued focus on health equity across several key domains and enhanced global data that reflect improved methods and incorporation of ≈3000 new data sources since last year's Statistical Update.

Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics.

The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Presently, colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. We provided global, regional, and national estimates of the burden of CRC and their attributable risks from 1990 to 2021, aiming to guide screening, early detection, and treatment strategies, optimize healthcare resource allocation, and facilitate the rational management of burden of CRC.

Using data derived from the Global Burden of Disease database, we estimated the incidence, mortality, and disability-adjusted life years (DALYs) of CRC. The temporal trends of the age-standardized rate of CRC were quantified by calculating the estimated annual percentage changes (EAPC). Deaths from CRC attributable to each risk factor that had evidence of causation with CRC were estimated. CRC's deaths and DALYs was forecast through 2050 by logistic regression with Socio-Demographic Index as a predictor, then multiplying by projected population estimates.

Globally, between 1990 and 2021, the incident cases, death cases, and DALYs attributed to CRC have doubled, the age-standardized incidence rate (ASIR) presented a slightly upward tendency, while the age-standardized death rate (ASMR) and the age-standardized DALYs rate (ASDR) exhibited a decreasing trend. From 1990-2021, the ASIR for males has an increased trend, while females presented a downward trend. The ASIR and ASDR of CRC were higher in high and high-middle sociodemographic index (SDI) countries. The ASIR of CRC in 165 countries and territories showed escalating trend. Globally, for males and both sexes combined, diet low in whole grains was the leading risk factor for age-standardized deaths from CRC in 2021. However, among females, diet low in milk was the leading risk factor. We forecast that 2.18 million (1.53-2.94) individuals will death for CRC worldwide by 2050, and the DALYs achieve 41.7 million (29.9-55.4) by 2050.

The doubling of incidence counts and mortality cases and the rising ASIR in most countries indicates a significant burden of CRC. Authorities should devise suitable measures to address the increasing burdens, such as optimizing screening programs, enhancing awareness and screening efforts for males, and reducing exposure to modifiable risk factors.

The purpose of this study was to look into any potential connections between the occurrence of colon cancer and the condition of the body of lipid accumulation product (LAP) index.

Using data from the 2009-2018 National Health and Nutrition Examination Survey (NHANES), we performed a cross-sectional analysis with 24,592 individuals. Utilizing multivariate logistic regression modelling, the relationship between LAP levels and colon cancer risk was investigated. Subgroup analysis, trend test, interaction test, and stratified smoothed curve were also carried out.

LAP levels and colon cancer risk were positively correlated after controlling for potential covariates (OR = 10.56, 95% CI: 2.40-46.53), the findings of trend tests are statistically significant. In particular groups, subgroup analysis revealed a positive connection between LAP levels and the risk of colon cancer. The association between LAP levels and colon cancer risk was shown to be M-shaped in the group under 60 years old, inverted V-shaped in the female and no-diabetes groups, and inverted L-shaped in the smoking and no-hypertensive groups, according to stratified smoothed curve fitting.

According to our findings, there is a strong correlation between LAP levels and the risk of colon cancer.

Type II diabetes mellitus (T2DM) has been associated with increased risk of colon cancer (CC) and worse prognosis in patients with metastases. The effects of T2DM on postoperative chemoresistance rate (CRR) and long-term disease-free survival (DFS) and overall survival (OS) in patients with stage III CC who receive curative resection remain controversial.

To investigate whether T2DM or glycemic control is associated with worse postoperative survival outcomes in stage III CC.

This retrospective cohort study included 278 patients aged 40-75 years who underwent surgery for stage III CC from 2018 to 2021. Based on preoperative T2DM history, the patients were categorized into non-DM (n = 160) and DM groups (n = 118). The latter was further divided into well-controlled (n = 73) and poorly controlled (n = 45) groups depending on the status of glycemic control. DFS, OS, and CRR were compared between the groups and Cox regression analysis was used to identify risk factors.

Patients in the DM and non-DM groups demonstrated similar DFS, OS, and CRR (DFS: 72.03% vs 78.75%, P = 0.178; OS: 81.36% vs 83.12%, P = 0.638; CRR: 14.41% vs 7.5%, P = 0.063). Poorly controlled DM was associated with a significantly worse prognosis and higher CRR than well-controlled DM (DFS: 62.22% vs 78.07%, P = 0.021; OS: 71.11% vs 87.67%, P = 0.011; CRR: 24.40% vs 8.22%, P = 0.015). High preoperative fasting plasma glucose [DFS: Hazard ratio (HR) = 2.684, P < 0.001; OS: HR = 2.105, P = 0.019; CRR: HR = 2.214, P = 0.005] and glycosylated hemoglobin levels (DFS: HR = 2.344, P = 0.006; OS: HR = 2.119, P = 0.021; CRR: HR = 2.449, P = 0.009) indicated significantly poor prognosis and high CRR, while T2DM history did not (DFS: HR = 1.178, P = 0.327; OS: HR = 0.933, P = 0.739; CRR: HR = 0.997, P = 0.581).

Increased preoperative fasting plasma glucose and glycosylated hemoglobin levels, but not T2DM history, were identified as risk factors associated with poor postoperative outcomes and high CRR in patients with stage III CC.

Cancer is a fatal disease with a high global prevalence and is associated with an increased incidence of metabolic disorders. This study aimed to develop a novel metabolic prognostic system to evaluate the overall metabolic disorder burden in cancer patients and its relationship with their prognosis. The patients in this study were enrolled from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) project. The least absolute shrinkage and selection operator (LASSO) analysis was used to screen for indicators of metabolic disorders. Cox regression analysis was used to evaluate the independent association between indicators of metabolic disorders and mortality in patients. The Kaplan-Meier method was used to evaluate the survival of patients with varying burdens of metabolic disorders. Finally, nomogram prognostic models and corresponding calculators were constructed and evaluated using the areas under the receiver operating characteristic curves (AUC), decision curve analysis (DCA), and calibration curves. Five of the 19 hematological indexes, including hemoglobin, neutrophils, direct bilirubin, albumin, and globulin, were selected as the evaluation indicators of metabolic disorder burden and independent risk factors for prognosis in cancer patients. Patients with a higher metabolic disorder burden had poorer survival rates. The AUC of the 1-year, 3-year, and 5-year overall survival of the prognostic nomogram was 0.678, 0.664, and 0.650, respectively. DCA and calibration curves indicated that the clinical benefit rate of metabolic disorder burden prognostic markers was high. Patients with a higher metabolic disorder burden had poorer survival rates. The nomogram and corresponding calculator can accurately evaluate the metabolic disorder burden and predict the prognosis of patients with cancer.

Colon cancer is a significant health concern, and obesity is a well-established risk factor. However, previous studies have mainly focused on assessing body weight as a risk factor for colon cancer at a specific time point. This nationwide cohort study investigated the association between body weight changes, which can fluctuate throughout an individual's lifespan, and the incidence of colon cancer using the South Korean population database provided by the National Health Insurance Service (NHIS). Participants who underwent biennial health screenings between 2004 and 2006, and had follow-up health check-ups between 2014 and 2016, were included in this study. Body weight changes were categorized as follows: < 5%, decrease 5-20%, decrease > 20%, increase 5-20%, or > 20%. The primary outcome was the incidence of newly diagnosed colon cancer. Statistical analysis was used to examine the relationship between body weight changes and the incidence of colon cancer stratified according to age and sex. The Kaplan-Meier method estimated the cumulative incidence of colon cancer, and Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI), adjusting for confounding factors. The analysis included data from 10,332,397 individuals, with a mean (± SD) age of 45.5 ± 13.1 years, and 54.9% were male. In males with a body mass index (BMI) range of 18-30 kg/m2, both a weight gain of 5-20% (HR 1.07, P > z 0.01 [95% CI 1.02-1.13]) and weight gain > 20% (HR 1.27, P > z 0.03 [95% CI 1.03-1.56]) were associated with an increased risk for colon cancer. In addition, males < 40 years of age exhibited a higher risk for colon cancer with > 20% weight gain (HR 1.65, P > z < 0.001 [95% CI 1.18-2.30]). Whereas, females within the BMI range of 18-30 kg/m2 who exhibited > 20% weight loss demonstrated a reduced risk (HR 0.77, P > z 0.04 [95% CI 0.60-0.98]). Moreover, females ≥ 40 years of age, who experienced weight loss > 20%, exhibited a decreased risk for colon cancer (HR 0.76; P > 0.02 [95% CI 0.60-0.96]). This nationwide cohort study demonstrated a relationship between body weight changes and the incidence of colon cancer, with differences based on sex and age. In particular, avoiding weight gain is crucial for males < 40 years of age, whereas weight loss could be beneficial for females > 40 years of age in reducing the risk of colon cancer.

The rapidly aging population is fueling a surge in diabetes, especially Type 2, which heightens colorectal cancer (CRC) risk. Colorectal adenoma, a precursor, compounds this trend. Although alpha-glucosidase inhibitors are effective hypoglycemic drugs working in the GI tract, the link between them and colorectal adenoma formation remains unexplored. A retrospective cross-sectional study was conducted on type 2 diabetes patients aged 60 and above using data from Wenzhou Central Hospital from January 2021 to May 2024. We used multivariable logistic regression and propensity score matching analysis (PSM) to calculate adjusted ORs for colorectal adenoma, controlling for potential confounders. A total of 311 subjects were enrolled in the study, with a mean age of 67.55 years. 138 (44.4%) were diagnosed with colorectal adenoma. Multivariate logistic regression analysis revealed that the AGI (Alpha-glucosidase inhibitor) Group had an adjusted OR of 0.399 (95% CI = 0.22-0.723, p = 0.002) compared to those with AGI free people. A similar trend was also observed in the PSM analysis (OR = 0.362, 95% CI = 0.176-0.744, p = 0.004). Subgroup analysis reveals hypertension as a potential modulator of the inverse relationship between AGI and colorectal adenoma occurrence post-PSM (p = 0.049). And AGI reduces serum iron levels, both before (p = 0.01) and after PSM (p = 0.028). In summary, our findings indicate that AGI significantly mitigates the risk of colorectal adenoma among individuals aged 60 and above, particularly among those afflicted with hypertension. Additionally, it substantially decreases serum iron levels.

Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors, including abdominal obesity, hyperglycemia, hypertension, and dyslipidemia. Gastric cancer (GC) is a common malignancy with significant mortality rates. The relationship between MetS and GC risk remains controversial. This systematic review and meta-analysis aimed to evaluate the correlation between MetS and GC.

Case-control studies investigating the association between MetS and GC were obtained from various databases, including China National Knowledge Infrastructure (CNKI), SinoMed, Embase, Web of Science, The Cochrane Library, and PubMed. The search was performed from the inception of each database up until September, 2023. Two researchers independently screened the literature, extracted data, and assessed the quality of the included studies. A meta-analysis of the included literature was conducted using Stata 12.0 software. The study protocol is registered in PROSPERO (CRD42023490410).

A total of eight studies involving a combined sample size of forty-four thousand eight hundred and seventy participants were included in the meta-analysis. The findings revealed that the risk of developing GC was not significantly associated with body mass index, triglycerides, hypertension, high fasting glucose, or MetS. However, it was found to be positively correlated with high-density lipoprotein cholesterol (OR = 1.69, 95%CI: 1.35-2.12).

This meta-analysis suggests that MetS is not significantly associated with an increased risk of GC. The risk of GC increases with the presence of individual MetS components, such as high-density lipoprotein cholesterol. Therefore, GC prevention strategies should include lifestyle modifications and targeted interventions to manage MetS and its components.

Colorectal cancer (CRC) is the third most common cancer worldwide and presents a significant challenge to public health. Metabolic syndrome (MetS) is a condition that is predominantly characterized by abdominal obesity and metabolic abnormalities such as hypertension, hyperglycemia, and hyperlipidemia, and it is one of the critical risk factors for CRC. Traditional anthropometric measures have limitations in accurately assessing the risk associated with abdominal obesity. This study aimed to investigate the association between "A Body Shape Index" (ABSI) and the risk of developing CRC among individuals with MetS utilizing data from the National Health and Nutrition Examination Survey (NHANES).

This cross-sectional study conducted a statistical analysis of all adult participants who met the diagnostic criteria for MetS in the NHANES data from 1999 to 2018. The ABSI was calculated to quantify abdominal obesity. ABSI is derived from a formula that incorporates waist circumference (WC), body mass index (BMI), and height, and is calculated as ABSI = WC / (BMI^(2/3) × Height^(1/2)). Multivariate logistic regression modeling was used to examine the independent association between ABSI and CRC incidence. Receiver Operating Characteristic (ROC) curves were employed to analyze the ability of ABSI compared to traditional metrics in identifying CRC risk.

This study involved 16,018 MetS patients with a mean age of 51.8 years, of whom 50.3% were male and 49.7% were female. Logistic regression adjusted for confounders revealed a significant association between an elevated ABSI and an increased risk of developing CRC (odds ratio (OR): 1.433, 95% confidence interval (CI): 1.116 to 1.841; P = 0.005). ROC analyses confirmed that the predictive accuracy of the ABSI for the risk of developing CRC area under the curve (AUC): (0.668, 95% CI: 0.624 to 0.713) surpassed that of traditional measurement methods.

Among individuals with MetS, the ABSI is linked to an elevated risk of developing CRC. Compared with traditional anthropometric indices, the ABSI is a superior predictive marker for the risk of developing CRC.

Growing studies have indicated an association between dietary factors and gastroesophageal reflux disease (GERD). However, whether these associations refer to a causal relationship and the potential mechanism by which dietary factors affect GERD is still unclear.

A two-step mendelian randomization analysis was performed to obtain causal estimates of dietary factors, blood lipids on GERD. Independent genetic variants associated with 13 kinds of dietary factors and 5 kinds of blood lipids at the genome-wide significance level were selected as instrumental variables. The summary statistics for GERD were obtained from European Bioinformatics Institute, including 129,080 cases and 473,524 controls. Inverse variance weighted was utilized as the main statistical method. MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis were performed to evaluate possible heterogeneity and pleiotropy. And the potential reverse causality was assessed using Steiger filtering.

The results of the inverse variance weighted method indicated that genetically predicted total pork intake (OR = 2.60, 95% CI: 1.21-5.58, p = 0.0143), total bread intake (OR = 0.68, 95% CI: 0.46-0.99, p = 0.0497), total cereal intake (OR = 0.42, 95% CI: 0.31-0.56, p = 2.98E-06), and total cheese intake (OR = 0.41, 95% CI: 0.27-0.61, p = 1.06E-05) were associated with the risk of GERD. Multivariable Mendelian randomization analysis also revealed a negative association between total cereal intake, total cheese intake and the risk of GERD, but the effect of total pork intake and total bread intake on GERD disappeared after adjustment of smoking, alcohol consumption, use of calcium channel blockers, BMI, physical activity levels, and biological sex (age adjusted). Furthermore, the concentration of low-density lipoprotein cholesterol (LDL-C) is negatively correlated with total cheese intake, which mediates the impact of total cheese intake on GERD. The proportion mediated by LDL-C is 2.27% (95%CI: 1.57%, 4.09%).

This study provides evidence that an increase in total cereal intake and total cheese intake will decrease the risk of GERD. Additionally, LDL-C mediates the causal effect of total cheese intake on GERD. These results provide new insights into the role of dietary factors and blood lipids in GERD, which is beneficial for disease prevention.

Colorectal cancer (CRC) is a common tumor type, and liver metastasis reduces the long-term survival in CRC patients. Natural killer (NK) cells play an important role in anti-tumor immunity. The aim of this study was to investigate the mechanism of miR-214-5p on NK cells in CRC liver metastasis. We collected clinical samples of CRC liver metastasis and nonmetastatic tissues and purchased the human NK cell lines NK92 and liver metastatic CRC cells KM12L4 for research. RT‒qPCR, Western blot, CCK-8, Transwell, and flow cytometry methods were used to evaluate the effect of miR-214-5p/USP27X/Bim pathway regulating NK cell activity on CRC liver metastasis. In addition, we also investigated the potential targets and regulatory mechanisms of the signaling pathway of miR-214-5p. In this study, we found that miR-214-5p was downregulated in CRC liver metastasis tissues. After transfection of miR-214-5p mimic, the activity of NK cells was significantly enhanced, and the proliferation and migration ability of CRC liver metastasis cells were inhibited, while inducing tumor cell apoptosis. Further research proved that USP27X is a potential target for miR-214-5p and upregulates Bim level through deubiquitination. In addition, miR-214-5p mimic reduced the level of USP27X and Bim, thereby enhancing the antitumor effect of NK cells. In conclusion, our research results show that miR-214-5p promotes the antitumor effect of NK cells by regulating the USP27X/Bim pathway, thereby inhibiting CRC liver metastasis. This finding reveals the important role of miR-214-5p in regulating the immune function of NK cells, and provides new ideas for developing new immunotherapy strategies.

The online version contains supplementary material available at 10.1007/s10616-024-00642-1.

Cancer incidence in young adults or those aged 15-49 years old has increased during the past decade. Knowledge about the risk factors for cancer-related deaths in young adults is limited, particularly in low- and middle-income countries (LMICs).

This analysis was based on the Hanoi Prospective Cohort Study, an ongoing study of 39,401 participants aged 15 or older in Northern Vietnam in the 2007-2019 period. A Cox proportional hazard regression model was used to calculate the hazard ratio (HR) and 95% confidence intervals (95% CIs) for the association between potential factors and the risk of cancer-related deaths.

With a median follow-up of 11.01 years, we identified 164 deaths in young adults out of 554 total deaths. Overall, family history of cancer (HR = 7.34; 95% CI: 3.30-16.36), drinking alcohol (HR = 1.82; 95% CI: 1.18-2.81), and smoking (HR = 2.22; 95% CI: 1.36-3.63) were found to be risk factors, while drinking coffee was found to be a protective factor (HR = 0.49; 95% CI: 0.24-1.00) for cancer-related deaths in young adults. Young male adults were found to be at a higher risk due to excessive cigarette smoking (HR = 1.91; 95% CI: 1.00-3.68) and alcohol consumption (HR = 2.15; 95% CI: 1.32-3.53) than those aged 50 years and older (HR = 1.36 and 95% CI: 0.96-1.93 and 1.27 and 95% CI: 0.97-1.67, respectively). The risk of death from cancer in women compared with men in the young population was twice as high as that in the older population (HR = 1.18 and 95% CI: 0.72-1.94 vs. 0.47 and 95% CI: 0.35-0.63, respectively).

Our data suggest that the young Vietnamese population is vulnerable to the risk of cancer-related deaths and that cancer in women will increase rapidly in the future.

Intermittent fasting (IF) holds promise for enhancing metabolic health. However, the optimum IF forms and their superiority over continuous energy restriction (CER) remain unclear due to disconnected findings.

We systematically searched PubMed, Embase, and the Cochrane databases for meta-analyses of randomized controlled trials (RCTs) investigating the association between IF and metabolic health outcomes. Subsequently, we performed an umbrella review and network meta-analysis (NMA) to evaluate the efficacy of different forms of IF (time-restricted eating (TRE), alternate-day fasting (ADF), and 5:2 diet (regular eating for 5 days and energy restriction for 2 days per week)) compared to CER and usual diets on metabolic health outcomes. To assess the certainty of both direct and indirect estimates, we employed the Confidence in Network Meta-Analysis (CINeMA) approach. Additionally, we calculated the surface under the cumulative ranking curve (SUCRA) for each dietary strategy to determine their ranking in terms of metabolic health benefits.

Ten of the best and non-redundant meta-analysis studies, involving 153 original studies and 9846 participants, were included. When considering direct evidence only, all IF forms significantly reduced body weight compared to usual diets. In NMA incorporating indirect evidence, all IF regimens also significantly reduced body weight compared to usual diets. In the SUCRA of NMA, IF ranked higher than usual diets or CER in 85.4% and 56.1% of the outcomes, respectively. ADF had the highest overall ranking for improving metabolic health (ranked first: 64.3%, ranked second: 14.3%).

Overall, all IF forms demonstrate potentials to improve metabolic health, with ADF appearing to produce better outcomes across investigated outcomes. Further high-quality trials are warranted to confirm the (relative) efficacy of IF on metabolic health.

PROSPERO (record no: CRD42022302690).

Colorectal cancer (CRC) is the most common gastrointestinal malignancy worldwide, with obesity-induced lipid metabolism disorders playing a crucial role in its progression. A complex connection exists between gut microbiota and the development of intestinal tumors through the microbiota metabolite pathway. Metabolic disorders frequently alter the gut microbiome, impairing immune and cellular functions and hastening cancer progression.

This study thoroughly examined the gut microbiota through 16S rRNA sequencing of fecal samples from 181 CRC patients, integrating preoperative Low-density lipoprotein cholesterol (LDL-C) levels and RNA sequencing data. The study includes a comparison of microbial diversity, differential microbiological analysis, exploration of the associations between microbiota, tumor microenvironment immune cells, and immune genes, enrichment analysis of potential biological functions of microbe-related host genes, and the prediction of LDL-C status through microorganisms.

The analysis revealed that differences in α and β diversity indices of intestinal microbiota in CRC patients were not statistically significant across different LDL-C metabolic states. Patients exhibited varying LDL-C metabolic conditions, leading to a bifurcation of their gut microbiota into two distinct clusters. Patients with LDL-C metabolic irregularities had higher concentrations of twelve gut microbiota, which were linked to various immune cells and immune-related genes, influencing tumor immunity. Under normal LDL-C metabolic conditions, the protective microorganism Anaerostipes_caccae was significantly negatively correlated with the GO Biological Process pathway involved in the negative regulation of the unfolded protein response in the endoplasmic reticulum. Both XGBoost and MLP models, developed using differential gut microbiota, could forecast LDL-C levels in CRC patients biologically.

The intestinal microbiota in CRC patients influences the LDL-C metabolic status. With elevated LDL-C levels, gut microbiota can regulate the function of immune cells and gene expression within the tumor microenvironment, affecting cancer-related pathways and promoting CRC progression. LDL-C and its associated gut microbiota could provide non-invasive markers for clinical evaluation and treatment of CRC patients.

The objective of this study is to evaluate the predictive ability of the TyG index for the presence of adenoma and multiple adenomas in an asymptomatic population.

A secondary analysis was conducted on a prospective cohort of asymptomatic subjects aged between 50 and 75 who underwent CRC screening. Fasting blood glucose (FBG) and lipid profiles were measured within three months prior colonoscopy. TyG index was estimated as ln [fasting triglycerides (mg/dL) × FBG (mg/dL)/2]. Multivariate logistic regression was performed to assess the association between the TyG index and the risk of adenoma. Its association with multiple adenomas (≥5) and the continuous number of adenomas were assessed by multinomial regression and log-normal linear regression, respectively.

A total of 1,538 subjects were recruited among which 876 subjects (57%) had at least one adenoma detected. Elevated TyG index was positively associated with the incidence of adenoma (adjusted odds ratio [aOR]: 1.26, 95% confidence interval [CI]: 1.04-1.54). Compared with the lowest TyG index (≤ 8) group, the risk of adenoma was the highest among subjects in the highest TyG index (> 10) group (aOR: 3.36, 95% CI: 1.44-7.73). As compared to the non-adenoma group, the TyG index was also positively associated with multiple adenomas (aOR: 1.74, 95% CI: 1.17-2.57), and the estimate was also the highest in the highest TyG group (aOR: 14.49, 95% CI: 3.12-67.20). As for the number of adenomas, the positive association was maintained (Estimates: 1.06, 95% CI: 1.01-1.12) while the number of adenomas increase the most in the highest TyG index group (Estimates: 1.35, 95% CI: 1.10-1.65).

Elevated TyG index is associated with an increased risk of colorectal adenoma and an increased number of adenomas for asymptomatic subjects aged ≥50.

This study was registered on clinicaltrials.gov (NCT03597204 and NCT04034953).

The global prevalence of Metabolic Syndrome (MetS) is increasing, primarily characterized by abdominal obesity, which significantly heightens the risk of cardiovascular diseases, gastrointestinal disorders, and cancers. Constipation is a common gastrointestinal issue that impacts both physiological and psychological health and worsens with age. Calcium, an essential mineral vital for human health, has been proven to be crucial not only for bone health but also beneficial for gastrointestinal health. However, the results regarding its impact on constipation are inconsistent. This study aimed to investigate the relationship between dietary calcium intake and constipation in individuals with MetS.

This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010. Participants were assessed for MetS based on the International Diabetes Federation (IDF) criteria. Dietary calcium intake was evaluated through 24-h dietary recalls, and constipation was defined based on the frequency of bowel movements recorded in the bowel health questionnaire. The relationship between calcium intake and constipation was explored using logistic regression models with adjustment for covariates, and restricted cubic spline analyses were also used to investigate nonlinear relationships.

The study included 4,838 adult participants with MetS. Adjusted logistic regression revealed that an increase in dietary calcium intake was significantly associated with a reduced risk of constipation (OR: 0.562, 95% CI: 0.379 to 0.835, p = 0.006). Compared to the lowest quartile, the highest quartile of dietary calcium intake significantly decreased the risk of constipation (OR: 0.282, 95% CI: 0.115 to 0.691, p = 0.008). Results from the restrictive cubic spline analysis indicated a negative linear association between dietary calcium intake and constipation risk (non-linearity p = 0.704).

The findings suggested that increased dietary calcium intake is associated with a decreased risk of constipation among MetS patients, emphasizing dietary calcium as a potentially modifiable factor for managing gastrointestinal symptoms in this population.

Merriam-Webster and Oxford define a xenobiotic as any substance foreign to living systems. Allura Red AC (a.k.a., E129; FD&C Red No. 40), a synthetic food dye extensively used in manufacturing ultra-processed foods and therefore highly prevalent in our food supply, falls under this category. The surge in synthetic food dye consumption during the 70s and 80s was followed by an epidemic of metabolic diseases and the emergence of early-onset colorectal cancer in the 1990s. This temporal association raises significant concerns, particularly given the widespread inclusion of synthetic food dyes in ultra-processed products, notably those marketed toward children. Given its interactions with key contributors to colorectal carcinogenesis such as inflammatory mediators, the microbiome, and DNA damage, there is growing interest in understanding Allura Red AC's potential impact on colon health as a putative carcinogen. This review discusses the history of Allura Red AC, current research on its effects on the colon and rectum, potential mechanisms underlying its impact on colon health, and provides future considerations. Indeed, although no governing agencies classify Allura Red AC as a carcinogen, its interaction with key guardians of carcinogenesis makes it suspect and worthy of further molecular investigation. The goal of this review is to inspire research into the impact of synthetic food dyes on colon health.

Prior antibiotic use may be a factor in the rising incidence of colorectal cancer seen in those under 50 years of age (early-onset colorectal cancer [EOCRC]); however, the few studies to examine this link have reported conflicting results. Therefore, we evaluated the association between oral antibiotic use in adulthood and EOCRC in a large integrated healthcare system in the United States.

A population-based nested case-control study was conducted among Kaiser Permanente Northern California patients 18-49 years of age diagnosed with EOCRC (adenocarcinoma of the colon or rectum) in 1998-2020 who had ≥2 years of continuous pharmacy benefit prior to diagnosis. Cases were matched 4:1 to healthy controls on birth year, sex, race and ethnicity, medical facility, and duration of pharmacy benefit. Antibiotic exposure >1 year before the diagnosis/index date was assessed using prescribing records. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals. A sensitivity analysis was performed among those with ≥10 years of continuous prescribing records.

A total of 1359 EOCRC cases were matched to 4711 healthy controls. Antibiotic use in adulthood was not significantly associated with EOCRC in unadjusted or adjusted analyses (adjusted odds ratio, 1.04; 95% confidence interval, 0.94-1.26). No associations were seen for cumulative number of oral antibiotic dispensations or for any prior period of antibiotic exposure.

In a large U.S. healthcare setting, there was no conclusive evidence of an association between oral antibiotic use in adulthood and risk of EOCRC.

The metabolic effects of metabolic syndrome (MetS) on musculoskeletal metabolism are controversial. This study explored the effect of MetS on bone mineral density (BMD) and muscle quality index (MQI).

Data from the NHANES database from 2011 to 2014 were extracted, and nonpregnant participants aged 45-59 years were included. The included data were first weighted by complex sampling, and then, the effect of MetS on BMD and MQI was analyzed using multifactorial linear regression. We then performed a stratified analysis by gender and BMI classification. Moreover, a mediation analysis of MetS on BMD was conducted, with MQI as a mediating variable. A propensity score matching analysis method with a complex sampling design was additionally performed to verify the stability of the results.

A total of 1943 participants were eventually included. After adjusting for covariates, the results of linear regression show that MetS is associated with elevated pelvic BMD (beta = 0.03; 95% CI = 0.01, 0.06; P=0.02) and reduced MQI, especially arm MQI (beta = -1.02; 95% CI = -1.27, -0.77; P < 0.0001). MetS is more associated with BMD in women, MQI in normal or heavyweight, and BMD in lightweight, according to stratified analysis. MQI explains the indirect effect of MetS on BMD (beta = 0.007; 95% CI = 0.003, 0.010).

This study provides evidence that MetS elevates BMD and reduces MQI, and further, that there is a mediating effect of MQI on elevated BMD.

Since the nineties, the incidence of sporadic early-onset (EO) cancers has been rising worldwide. The underlying reasons are still unknown. However, identifying them is vital for advancing both prevention and intervention. Here, we exploit available knowledge derived from clinical observations to formulate testable hypotheses aimed at defining the causal factors of this epidemic and discuss how to experimentally test them. We explore the potential impact of exposome changes from the millennials to contemporary young generations, considering both environmental exposures and enhanced susceptibilities to EO-cancer development. We emphasize how establishing the time required for an EO cancer to develop is relevant to defining future screening strategies. Finally, we discuss the importance of integrating multi-dimensional data from international collaborations to generate comprehensive knowledge and translate these findings back into clinical practice.

Inflammation plays a crucial role in the development of metabolic syndrome (MetS). However, the roles of pepsinogens (PGs) and gastrin, known biomarkers linked to gastric inflammation, in MetS and the transition of MetS status are unclear. This research aimed to explore the relationship between MetS, the transition of MetS status, and levels of gastric biomarkers.

This large-scale cross-sectional study included 19162 participants aged 18-80 years between August 2021 and March 2024. Serum levels of the gastric biomarkers PGI, PGII, and gastrin-17 were analyzed using enzyme-linked immunosorbent assay. In addition, the relationship between transitions of MetS status based on 1032 MetS-negative participants from baseline to the second health exam after 2 years was considered. The association between MetS and the transitions of MetS status and gastric biomarkers was analyzed using logistic regression models.

The prevalence of MetS in the study population was 31.4%, with higher rates in males (35.2%) than females (24.6%). Gastrin-17 levels were markedly elevated in participants with MetS, a trend observed in both genders. In the logistic regression analysis, after adjusting for confounding factors, gastrin-17 levels were strongly and positively correlated with MetS in the entire cohort and in males but not in females. Male participants with MetS had lower levels of PGI and PGII than those without MetS, whereas the opposite trend was observed in females. Logistic regression analysis indicated that PGI and PGII were not independently associated with MetS. During the follow-up of 2 years, 199 (19.28%) of the 1032 MetS-negative participants transitioned to MetS-positive status. As compared to the stable MetS-negative subjects, transition from MetS-negative to MetS-positive was associated with higher levels of gastrin-17, especially in males, but not in females.

Gastrin-17 is a promising biomarker for MetS, exhibiting potential utility in monitoring the transition of MetS status and revealing gender difference.

(1) Background: Young-onset colorectal adenomas (YOAs) are precursors to early-onset colorectal cancer, a growing concern among individuals under 50 years old. This study investigated the association between surrogate markers of insulin resistance (IR) and YOAs occurrence. (2) Methods: A retrospective cross-sectional analysis was conducted on 4467 individuals aged 20 to 49 years who underwent their first screening colonoscopy at Dong-A University Hospital from 2018 to 2022. IR was assessed using the triglyceride-glucose (TyG) index, triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-C), and metabolic score for insulin resistance (METS-IR). (3) Results: Individuals with YOAs exhibited significantly higher median TyG index (8.51 ± 0.71 vs. 8.32 ± 0.61, p < 0.001), TG/HDL-C ratio (2.78 ± 3.05 vs. 2.12 ± 1.85, p < 0.001), and METS-IR (35.72 ± 8.37 vs. 33.44 ± 9.11, p < 0.001) values than controls. The adjusted odds ratios for YOAs were 1.064 (95% CI: 1.22-2.23, p = 0.021) for the TyG index, 1.067 (95% CI: 1.031-1.105, p < 0.001) for the TG/HDL-C ratio, and 1.011 (95% CI: 1.002-1.021, p = 0.023) for METS-IR values, indicating a strong association between higher IR marker values and the presence of YOAs. (4) Conclusions: Elevated IR marker values are strongly associated with the occurrence of YOAs in individuals under 50 years old.

To investigate the role of body mass index (BMI), serum lipid profile molecules and their derivative indexes in colorectal polyps.

A total of 352 individuals who underwent colonoscopy at our center were included in this retrospective analysis. Of these, 247 patients without evident abnormalities (control group), while 105 patients diagnosed with colorectal polyps (patient group). Serum lipid profile molecules and their derivative indexes were then compared between the two groups.

The patient group exhibited significantly higher levels of total cholesterol (TC) and apolipoprotein B (ApoB) compared to the control group (p<0.05). In males, the patient group displayed elevated levels of ApoB and ApoB/ApoA1 ratio compared to the control group (p<0.05). Additionally, the triglycerides (TG) and TG/high-density lipoprotein-cholesterol (HDL-C) ratios were significantly higher in the multiple polyps group than in the single polyp group (p<0.05). Furthermore, the HDL-C and HDL-C/ApoA1 ratio levels were higher in the adenomatous polyp group when compared to the non-adenomatous polyp group (p<0.05). Multiple logistic regression analysis indicated that total cholesterol (TC), TG, low-density lipoprotein-cholesterol (LDL-C), TC/HDL-C ratio, TG/HDL-C ratio and LDL-C/HDL-C ratio were risk factors for the occurrence of colorectal polyps (p<0.05). ROC curve analyses revealed that TC, ApoB, and ApoB/ApoA1 ratio were associated with colorectal polyps. No significant difference in BMI between the two groups (p>0.05).

The incidence and progression of colorectal polyps are linked to serum lipid molecules and their derivative indexes. Dyslipidemia may increase the risk of colorectal polyps, potentially leading to colorectal cancer (CRC).

Mitochondrial dysfunction, characterized by elevated oxidative stress, impaired energy balance, and dysregulated mitochondrial dynamics, is a hallmark of metabolic syndrome (MetS) and its comorbidities. Ferulic acid (FA), a principal phenolic compound found in whole grains, has demonstrated potential in ameliorating oxidative stress and preserving energy homeostasis. However, the influence of FA on mitochondrial health within the context of MetS remains unexplored. Moreover, the impact of FA on autophagy, which is essential for maintaining energy homeostasis and mitochondrial integrity, is not fully understood. Here, we aimed to study the mechanisms of action of FA in regulating mitochondrial health and autophagy using palmitate-treated HepG2 hepatocytes as a MetS cell model. We found that FA improved mitochondrial health by restoring redox balance and optimizing mitochondrial dynamics, including biogenesis and the fusion/fission ratio. Additionally, FA was shown to recover autophagy and activate AMPK-related cell signaling. Our results provide new insights into the therapeutic potential of FA as a mitochondria-targeting agent for the prevention and treatment of MetS.

Colorectal cancer (CRC) affects approximately 2 million people worldwide. Obesity is the major risk factor for CRC. In addition, obesity contributes to a chronic inflammatory stage that enhances tumor progression through the secretion of proinflammatory cytokines. In addition to an increased inflammatory response, obesity-associated cancer presents accrued molecular factors related to cancer characteristics, such as genome instability, sustained cell proliferation, telomere dysfunctions, angiogenesis, and microbial alteration, among others. Despite the evidence accumulated over the last few years, the treatments for obesity-associated CRC do not differ from the CRC treatments in normal-weight individuals. In this review, we summarize the current knowledge on obesity-associated cancer, including its epidemiology, risk factors, molecular factors, and current treatments. Finally, we enumerate possible new therapeutic targets that may improve the conditions of obese CRC patients. Obesity is key for the development of CRC, and treatments resulting in the reversal of obesity should be considered as a strategy for improving antineoplastic CRC therapies.

Despite decreased incidence rates in average-age onset patients in high-income economies, colorectal cancer is the third most diagnosed cancer in the world, with increasing rates in emerging economies. Furthermore, early onset colorectal cancer (age ≤50 years) is of increasing concern globally. Over the past decade, research advances have increased biological knowledge, treatment options, and overall survival rates. The increase in life expectancy is attributed to an increase in effective systemic therapy, improved treatment selection, and expanded locoregional surgical options. Ongoing developments are focused on the role of sphincter preservation, precision oncology for molecular alterations, use of circulating tumour DNA, analysis of the gut microbiome, as well as the role of locoregional strategies for colorectal cancer liver metastases. This overview is to provide a general multidisciplinary perspective of clinical advances in colorectal cancer.

Infrared spectroscopy is a powerful technique for probing the molecular profiles of complex biofluids, offering a promising avenue for high-throughput in vitro diagnostics. While several studies showcased its potential in detecting health conditions, a large-scale analysis of a naturally heterogeneous potential patient population has not been attempted. Using a population-based cohort, here we analyze 5,184 blood plasma samples from 3,169 individuals using Fourier transform infrared (FTIR) spectroscopy. Applying a multi-task classification to distinguish between dyslipidemia, hypertension, prediabetes, type 2 diabetes, and healthy states, we find that the approach can accurately single out healthy individuals and characterize chronic multimorbid states. We further identify the capacity to forecast the development of metabolic syndrome years in advance of onset. Dataset-independent testing confirms the robustness of infrared signatures against variations in sample handling, storage time, and measurement regimes. This study provides the framework that establishes infrared molecular fingerprinting as an efficient modality for populational health diagnostics.

Background/Objectives: Perinatal exposure to malnutrition has been hypothesised to influence the development of young-onset cancer (≤50 years of age). This study aimed to determine if perinatal malnutrition in individuals exposed to the Great Famine of China increased their risk of developing young-onset cancer compared to other individuals born prior to the famine. Subjects/Methods: This cross-sectional study involved 7272 participants from the China Health and Nutrition Survey who were classified into four groups based on birth year: participants born between 1953 and 1955 (before the famine) were designated as the pre-famine group (unexposed); the remainder formed perinatal exposure groups comprised of those exposed during the famine (1959-1961), those exposed in the early post-famine period (1962-1964), and those exposed in the late post-famine period (1965-1967). Multivariable adjusted log-binomial regression models were used to calculate the RR and 95% CI of young-onset cancer (including genitourinary cancer) across four groups. Results: Perinatal exposure to early post-famine (RR 2.08; 95%CI 1.04, 4.34; p = 0.043) and the female sex (RR 15.6, 95%CI 4.54, 60.3; p < 0.001) were noted to have a significantly increased risk of young-onset cancer. In addition, the early (RR 13.8; 95%CI 2.68, 253; p = 0.012) and late post-famine (RR 12.3; 95%CI 2.16, 231; p = 0.020) cohorts demonstrated a significantly increased risk of young-onset genitourinary cancer. The latter was accompanied by an increased risk of hypertension (RR 3.30; 95%CI 1.28, 7.87; p = 0.009). Conclusions: Perinatal exposure to famine, especially in females, was associated with a higher risk of young-onset cancer. This was particularly evident for young-onset genitourinary cancers. These findings highlight the potential long-term impact of perinatal malnutrition on young-onset carcinogenesis.

The relationship between aspirin usage and the risk of colorectal cancer (CRC) among individuals with both hypertension (HTN) and diabetes mellitus (DM) remains unclear. This study aims to explore the impact of aspirin use on the site-specific CRC risk in patients with metabolic comorbidity.

A case-control study was conducted among 1,331 CRC patients and 2,771 controls recruited from the Nation Cancer Center in Korea. Multinomial logistic regression analyses were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between aspirin use, metabolic disease status, and site-specific CRC risk.

Among the 4,102 participants, 1,191 individuals had neither HTN nor DM, 2,044 were diagnosed with HTN, 203 with DM, and 664 presented with HTN and DM comorbidity. An increasing number of HTN and DM was associated with an increased risk of overall CRC (HTN or DM: OR, 1.70; 95% CI, 1.39-2.07; HTN and DM: OR, 8.43; 95% CI, 6.37-11.16), while aspirin use was associated with a decreased risk of overall CRC (OR, 0.31; 95% CI, 0.21-0.46). These results remained consistent across anatomical sites. Among individuals with HTN and DM comorbidity, aspirin use notably associated with lower risk of overall CRC (OR, 0.39; 95% CI, 0.21-0.72), proximal colon (OR, 0.32; 95% CI, 0.13-0.71) and rectal cancer (OR, 0.27; 95% CI, 0.08-0.97), but not distal colon cancer (OR, 0.58; 95% CI, 0.27-1.24).

This study showed that aspirin use is negatively associated with overall and site-specific CRC, even among individuals with HTN and DM comorbidity.

The prevalence of metabolic diseases is increasing worldwide and is influenced by multiple environmental, psychological, and dietary factors. As overseas deployment (OD) of Korean soldiers brings about changes in these factors, this study aimed to explore the impact of OD on metabolic diseases.

We collected paired health checkup data of Korean soldiers between January 2020 and December 2022, before and after their deployment. We analyzed changes in lipid profile, fasting glucose, and liver function biomarkers during OD and compared the prevalence of metabolic diseases before and after the OD.

A total of 2,953 soldiers were enrolled. During OD, body weight, body mass index, total cholesterol, low-density lipoprotein, and fasting glucose levels decreased significantly. Furthermore, the prevalence of obesity, impaired fasting glucose, and nonalcoholic fatty liver disease decreased significantly from 45.78% to 33.49%, P < .001; 38.60% to 34.41%, P < .001; and 24.89% to 18.88%, P < .001, respectively. In a subgroup analysis of participants with long-term deployment (duration >365 days), only the prevalence of obesity decreased significantly during deployment, whereas the prevalence of hypertension and dyslipidemia increased.

Metabolic biomarkers improved, and the prevalence of metabolic diseases decreased significantly during OD. However, personnel with long-term deployment did not experience significant improvements in these parameters. Further analysis is needed to identify the factors influencing these discrepancies.

The incidence of colorectal cancer (CRC) is closely linked to metabolic diseases. Accumulating evidence suggests the regulatory role of AMP-activated protein kinase (AMPK) in cancer metabolic reprogramming. In this study, wild-type and AMPK knockout mice were subjected to azoxymethane-induced and dextran sulfate sodium (AOM/DSS)-promoted colitis-associated CRC induction. A stable AMPK-deficient Caco-2 cell line was also established for the mechanistic studies. The data showed that AMPK deficiency accelerated CRC development, characterized by increased tumor number, tumor size, and hyperplasia in AOM/DSS-treated mice. The aggravated colorectal tumorigenesis resulting from AMPK ablation was associated with reduced α-ketoglutarate production and ten-eleven translocation hydroxylase 2 (TET2) transcription, correlated with the reduced mismatch repair protein mutL homolog 1 (MLH1) protein. Furthermore, in AMPK-deficient Caco-2 cells, the mRNA expression of mismatch repair and tumor suppressor genes, intracellular α-ketoglutarate, and the protein level of TET2 were also downregulated. AMPK deficiency also increased hypermethylation in the CpG islands of Mlh1 in both colonic tissues and Caco-2 cells. In conclusion, AMPK deficiency leads to reduced α-ketoglutarate concentration and elevates the suppressive epigenetic modifications of tumor suppressor genes in gut epithelial cells, thereby increasing the risk of colorectal tumorigenesis. Given the modifiable nature of AMPK activity, it holds promise as a prospective molecular target for the prevention and treatment of CRC.

In recent years, the incidence of colorectal cancer (CRC) has been increasing. With the popularization of endoscopic technology, a number of early CRC has been diagnosed. However, despite current treatment methods, some patients with early CRC still experience postoperative recurrence and metastasis.

To search for indicators associated with early CRC recurrence and metastasis to identify high-risk populations.

A total of 513 patients with pT2N0M0 or pT3N0M0 CRC were retrospectively enrolled in this study. Results of blood routine test, liver and kidney function tests and tumor markers were collected before surgery. Patients were followed up through disease-specific database and telephone interviews. Tumor recurrence, metastasis or death were used as the end point of study to find the risk factors and predictive value related to early CRC recurrence and metastasis.

We comprehensively compared the predictive value of preoperative blood routine, blood biochemistry and tumor markers for disease-free survival (DFS) and overall survival (OS) of CRC. Cox multivariate analysis demonstrated that low platelet count was significantly associated with poor DFS [hazard ratio (HR) = 0.995, 95% confidence interval (CI): 0.991-0.999, P = 0.015], while serum carcinoembryonic antigen (CEA) level (HR = 1.008, 95%CI: 1.001-1.016, P = 0.027) and serum total cholesterol level (HR = 1.538, 95%CI: 1.026-2.305, P = 0.037) were independent risk factors for OS. The cutoff value of serum CEA level for predicting OS was 2.74 ng/mL. Although the OS of CRC patients with serum CEA higher than the cutoff value was worse than those with lower CEA level, the difference between the two groups was not statistically significant (P = 0.075).

For patients with T2N0M0 or T3N0M0 CRC, preoperative platelet count was a protective factor for DFS, while serum CEA level was an independent risk factor for OS. Given that these measures are easier to detect and more acceptable to patients, they may have broader applications.

The incidence of early-onset colorectal cancer (EOCRC; diagnosed <50 years of age) is rising globally; however, the causes underlying this trend are largely unknown. CRC has strong genetic and environmental determinants, yet common genetic variants and causal modifiable risk factors underlying EOCRC are unknown. We conducted the first EOCRC-specific genome-wide association study (GWAS) and Mendelian randomization (MR) analyses to explore germline genetic and causal modifiable risk factors associated with EOCRC.

We conducted a GWAS meta-analysis of 6176 EOCRC cases and 65 829 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT), the Colon Cancer Family Registry (CCFR), and the UK Biobank. We then used the EOCRC GWAS to investigate 28 modifiable risk factors using two-sample MR.

We found two novel risk loci for EOCRC at 1p34.1 and 4p15.33, which were not previously associated with CRC risk. We identified a deleterious coding variant (rs36053993, G396D) at polyposis-associated DNA repair gene MUTYH (odds ratio 1.80, 95% confidence interval 1.47-2.22) but show that most of the common genetic susceptibility was from noncoding signals enriched in epigenetic markers present in gastrointestinal tract cells. We identified new EOCRC-susceptibility genes, and in addition to pathways such as transforming growth factor (TGF) β, suppressor of Mothers Against Decapentaplegic (SMAD), bone morphogenetic protein (BMP) and phosphatidylinositol kinase (PI3K) signaling, our study highlights a role for insulin signaling and immune/infection-related pathways in EOCRC. In our MR analyses, we found novel evidence of probable causal associations for higher levels of body size and metabolic factors-such as body fat percentage, waist circumference, waist-to-hip ratio, basal metabolic rate, and fasting insulin-higher alcohol drinking, and lower education attainment with increased EOCRC risk.

Our novel findings indicate inherited susceptibility to EOCRC and suggest modifiable lifestyle and metabolic targets that could also be used to risk-stratify individuals for personalized screening strategies or other interventions.