Metabolic syndrome (MetS) is defined by the presence of at least three of five clinical parameters including abdominal obesity, insulin resistance, elevated triglycerides, reduced high-density lipoprotein (HDL) and hypertension. Major features describing MetS have been recognized risk factors for cancer onset, with an alarming impact on gastrointestinal (GI) tumors. Intriguingly, therapeutic administration of drugs to improve glycemic control and dyslipidemia (including metformin, statins) has been shown to have a preventive role in the development and in prognosis improvement of several cancer types. Overall, these observations highlight the key role of altered metabolism prevalently in cancer risk development and unveil anti-MetS agent repurposing potential beyond their conventional pharmacological action. The objective of this review is to summarize the current knowledge about the antitumor activity of anti-diabetic and anti-lipemic agents in GI cancer onset and progression. Here, pre-clinical evidence of their therapeutic potential and of their integration in novel compelling therapeutic strategies will be discussed. Possible clinical outcomes of these novel therapeutic combined protocols specifically dedicated to GI cancer patients will be put under the spotlight. In the future, these novel therapeutic options should be considered to improve conventional chemotherapy response and prognosis of this group of patients.

The role of specific lipids in colorectal cancer (CRC) incidence remains unclear. We aimed to evaluate associations of plasma lipids with CRC risk and the modification effects of common risk factors and ambient particulate matter (PM) exposure. We conducted a nested case-control study within the Dongfeng-Tongji cohort, including 218 cases and 436 matched controls. Plasma levels of 155 lipids were determined by UPLC-MS/MS. The conditional logistic regression and LASSO regression identified nine lipids as potential CRC risk biomarkers. Specifically, triacylglycerol (TAG) 56:7 [20:4], cholesterol ester (CE) 20:2 (1), CE 22:5, lysophosphatidylethanolamine (LPE) 18:2, and sphingomyelin (SM) 32:2 were associated with decreased CRC risk (adjusted ORs per SD: 0.05-0.68), while LPE 18:0, diglycerol (DAG) 16:1/17:1, SM 38:1, and SM 34:0 were associated with increased CRC risk (ORs per SD: 1.60-6.19). Compared to the traditional factors, these lipids exerted improvement of 35.4% in area under the curve (AUC) discriminations for CRC (AUC = 0.972 vs. 0.618). Notably, the associations between specific lipids and CRC risk were modified by BMI (TAG 56:7 [20:4]), smoking (LPE 18:0, DAG 16:1/17:1), alcohol consumption (SM 32:2), healthy diet (TAG 56:7 [20:4]), and PM exposure (TAG 56:7 [20:4], DAG 16:1/17:1, SM 38:1, LPE 18:2) (all Pinteraction <0.05). Our study identified 9 plasma lipids with significant associations with CRC risk and underscored the effect modifications of common risk factors and PM exposure on these associations. These findings provide new insights into the links between specific lipids and CRC development.

Liquid biopsies are an emerging, noninvasive tool for cancer diagnostics, utilizing biological fluids for molecular profiling. Nevertheless, the current methods often lack the sensitivity and specificity necessary for early detection and real-time monitoring. This work explores an advanced approach to improving liquid biopsy techniques through machine learning analysis of the Raman spectra measured to classify distinct exosome solutions by their cancer origin. This was accomplished by conducting principal component analysis (PCA) of the Raman spectra of exosomes from three cancer cell lines (COLO205, A375, and LNCaP) to extract chemically significant features. This reduced set of features was then utilized to train a linear discriminant analysis (LDA) classifier to predict the source of the exosomes. Furthermore, we investigated differences in the lipid composition in these exosomes by their spectra. This spectral similarity analysis revealed differences in lipid profiles between the different cancer cell lines as well as identified the predominant lipids across all exosomes. Our PCA-LDA framework achieved 93.3% overall accuracy and F1 scores of 98.2%, 91.1%, and 91.0% for COLO205, A375, and LNCaP, respectively. Our results from spectral similarity analysis were also shown to support previous findings of lipid dynamics due to cancer pathology and pertaining to exosome function and structure. These findings underscore the benefits of enhancing Raman spectroscopy analysis with machine learning, laying the groundwork for the development of early noninvasive cancer diagnostics and personalized treatment strategies. This work potentially establishes the foundation for refining the classification model and optimizing exosome extraction and detection from clinical samples for clinical translation.

Although the link between cardiovascular disease (CVD) and various cancers is well-established, the relationship between CVD risk and colorectal cancer (CRC) remains underexplored.

To elucidate the relationship between CVD risk scores and CRC incidence.

In this population-based cohort study, participants from the 2009 National Health Checkup were followed-up until 2020. The cardiovascular (CV) risk score was calculated as the sum of risk factors (age, family history of coronary artery disease, hypertension, smoking status, and high-density lipoprotein levels) with high-density lipoprotein (≥ 60 mg/dL) reducing the risk score by one. The primary outcome was incidence of newly diagnosed CRC.

Among 2526628 individuals, 30329 developed CRC during a mean follow-up of 10.1 years. Categorized by CV risk scores (0, 1, 2, and ≥ 3). CRC risk increased with higher CV risk scores after adjusting for covariates [(hazard ratio = 1.155, 95% confidence interval: 1.107-1.205) in risk score ≥ 3, P < 0.001]. This association was exclusively observed in males, most notably in the younger cohort (< 50 years) and was more pronounced in individuals not using statins. Moreover, even in participants without diabetes, a higher CV risk was associated with an increased CRC risk.

Increased CV risk scores were significantly associated with higher CRC risk, especially among males, younger populations, and non-statin users. Thus, males with a higher CV risk score, even at a younger age, are recommended to control their risk factors and undergo individualized CRC screening.

Dyslipidemia and statin use are associated with an increased risk of various cancers. However, the association in head and neck cancer (HNC) remains unclear. Therefore, this study aimed to investigate the impact of dyslipidemia and statin use on the development of HNC.

Using data from the Korean National Health Insurance Service-National Sample Cohort from 2002 to 2019, we compared two groups HNC patients (n = 1006) and matched control participants (n = 4024) after propensity score overlap weighted balancing. The odds ratios (ORs) for HNC development according to dyslipidemia and statin use duration were assessed using propensity score overlap-weighted multivariable logistic regression.

Individuals with untreated dyslipidemia had significantly lower odds of developing HNC than those of normal participants (OR 0.70, 95% confidence interval [CI] 0.59-0.82). Conversely, patients with dyslipidemia who received statin therapy (< 60 days) showed a nearly two-fold increase in the odds of HNC (OR 1.94, 95% CI 1.29-2.90). Long-term statin use (≥ 60 days) aligned the odds with those of normal participants (OR 0.89, 95% CI 0.76-1.04).

The adverse effect of short-term statin use on HNC development requires further study, and long-term statin use for dyslipidemia treatment does not increase the odds of HNC.

Background: Colorectal cancer (CRC) remains a global health challenge. Metabolic disorders, including dyslipidemia, have been linked to CRC progression, yet the relationship between lipid profiles, tumor location, and survival outcomes remains controversial. This study investigates the association between blood lipid parameters, tumor localization, and survival in CRC patients. Methods: A retrospective analysis was conducted on 126 CRC patients diagnosed between 2017 and 2024 at Kartal Dr. Lütfi Kırdar City Hospital. Patients with comorbidities affecting lipid metabolism or who were on lipid-lowering drugs were excluded. Clinical, pathological, and lipid data, including total cholesterol (TC), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and carcinoembryonic antigen (CEA), were analyzed. Tumor location was categorized as right-sided or left-sided. Overall survival (OS) was evaluated with a statistical analysis using Kaplan-Meier and Cox regression models. Results: Higher HDL-C levels and a lower TC/HDL-C ratio were significantly associated with improved OS (p: 0.004 and p: 0.016, respectively). This relationship remained significant in early- and advanced-stage disease (p: 0.04 for HDL-C and p: 0.03 for TC/HDL-C). In patients with tumors located in the right colon, LDL-C levels of 150 mg/dL and below were found to be statistically positively correlated with overall survival, while in patients with tumors located in the left colon, HDL-C levels of 45 mg/dL and above and TC/HDL-C levels of 4.16 and above were found to be statistically positively correlated with overall survival. A multivariate analysis confirmed that age, stage, HDL-C, and TC/HDL-C were independent predictors of OS. Conclusions: Our study highlights the potential role of lipid profiles, particularly HDL-C and the TC/HDL-C ratio, as prognostic factors in CRC. Further research, including molecular and genetic analyses, is needed to better understand the mechanisms underlying the relationship between lipid metabolism and CRC progression.

Current evidence on relationships between serum lipid biomarkers and the risk of gastrointestinal cancers remains controversial, with no consensus reached.

We conducted a prospective cohort study within the Kailuan Cohort wherein 88,225 individuals with baseline information on triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) was followed from 2006 to 2021 for the incidence of esophageal cancer (EC), gastric cancer (GC), and colorectal cancer (CRC). Cox proportional hazards models and restricted cubic spline (RCS) analysis were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Increased EC risk was associated with high HDL-C levels (HRQ4vs.Q1 = 2.50, 95% CI: 1.57-3.98), while a U-shaped relationship between HDL-C and EC risk was revealed in the RCS analysis (poverall ≤ 0.0001, pnonlinear = 0.02). No robust association was identified between lipid biomarkers and GC risk. In multivariable analysis, increased CRC risk was positively associated with high TC levels (HRQ4vs.Q1 = 1.42, 95% CI: 1.11-1.83, ptrend = 0.03), dose-responsely negatively associated with LDL-C levels over quartiles (HRQ2vs.Q1 = 0.83, 95% CI: 0.66-1.02; HRQ3vs.Q1 = 0.86, 95% CI: 0.69-1.07; HRQ4vs.Q1 = 0.68, 95% CI: 0.53-0.86, ptrend = 0.02), and showed a diminished negative association with HDL-C levels over quartiles (HRQ2vs.Q1 = 0.75, 95% CI: 0.60-0.94; HRQ3vs.Q1 = 0.76, 95% CI: 0.61-0.95; HRQ4vs.Q1 = 0.91, 95% CI 0.74-1.13, ptrend = 0.02). The subsequent RCS analysis revealed a linear negative relationship of LDL-C (poverall = 0.004, pnonlinear = 0.67) and a U-shaped relationship of HDL-C (poverall = 0.05, pnonlinear = 0.02) with CRC risk. Competitive risk analysis and sensitivity analysis confirmed the stability of our results.

We observed a U-shaped relationship regarding HDL-C levels with EC and CRC risk, and a linear inverse relationship between LDL-C levels and CRC risk. Relevant serum lipid levels should be properly managed in high-risk individuals of certain gastrointestinal cancers.

The association between metabolic factors and colorectal cancer (CRC) risk is inconclusive. This umbrella review aimed to summarise and describe the association using existing systematic reviews and/or meta-analyses.

Four databases (Medline, Scopus, Web of Science, and Cochrane Library) were searched for systematic reviews and/or meta-analyses of observational studies. Two independent authors extracted data on the summary estimated effect and heterogeneity of studies using I2 from the individual reviews. The Assessing the Methodological Quality of Systematic Reviews (AMSTAR 2) tool was used to evaluate the methodological quality.

49 articles were included in this review. Although most included studies were graded with critically low methodological quality (81.6 %), we found a significant positive association between obesity (summary relative risk (SRR) range 1.19-1.49), diabetes mellitus (SRR range 1.20-1.37), hypertension (SRR range 1.07-1.62), metabolic syndrome (SRR range 1.25-1.36), non-alcoholic fatty liver disease (pooled odds ratio (POR) range 1.13-1.56), and risk of CRC. Higher serum high-density lipoprotein cholesterol levels were associated with a lower risk of CRC in 3/6 reviews, while others did not find any association. There was no clear association between high triglyceride levels, total cholesterol levels, low-density lipoprotein cholesterol levels, and risk of CRC.

This umbrella review identified that most metabolic factors are significantly associated with increased risk of CRC. Thus, people affected by metabolic factors may be benefited from CRC screening and surveillance.

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.

Cardiovascular disease (CVD) and cancer are among the leading causes of morbidity and mortality globally, and these conditions are increasingly recognized to be fundamentally interconnected. In this Review, we present the current epidemiological data for each of the modifiable risk factors shared by the two diseases, including hypertension, hyperlipidaemia, diabetes mellitus, obesity, smoking, diet, physical activity and the social determinants of health. We then review the epidemiological data demonstrating the increased risk of CVD in patients with cancer, as well as the increased risk of cancer in patients with CVD. We also discuss the shared mechanisms implicated in the development of these conditions, highlighting their inherent bidirectional relationship. We conclude with a perspective on future research directions for the field of cardio-oncology to advance the care of patients with CVD and cancer.

We examined the role of psychological well-being related measures in explaining the associations between obesity and increased risk of non-communicable diseases (NCDs: hypertension, heart disease, stroke, diabetes, arthritis, cancer, and memory-related disease) in older adults.

Data were from the English Longitudinal Study of Ageing (ELSA), UK (baseline: Wave 4-2008/2009; n = 8127) and the Health and Retirement Study (HRS), US (baseline: Waves 9 and 10-2008/2010; n = 12,477). Objective body mass index was used to define obesity. A range of psychological well-being related measures (e.g., depressive symptoms, life satisfaction) was available in ELSA (n = 7) and HRS (n = 15), and an index of overall psychological well-being was developed separately in each study. NCDs were from a self-reported doctor diagnosis and/or other assessments (e.g., biomarker data) in both studies; and in ELSA, NCDs from linked hospital admissions data were examined. Longitudinal associations between obesity status, psychological well-being measures, and NCDs were examined using Cox proportional hazard models (individual NCDs) and Poisson regression (a cumulative number of NCDs). Mediation by psychological well-being related measures was assessed using causal mediation analysis.

Obesity was consistently associated with an increased prospective risk of hypertension, heart disease, diabetes, arthritis, and a cumulative number of NCDs in both ELSA and HRS. Worse overall psychological well-being (index measure) and some individual psychological well-being related measures were associated with an increased prospective risk of heart disease, stroke, arthritis, memory-related disease, and a cumulative number of NCDs across studies. Findings from mediation analyses showed that neither the index of overall psychological well-being nor any individual psychological well-being related measures explained (mediated) why obesity increased the risk of developing NCDs in both studies.

Obesity and psychological well-being may independently and additively increase the risk of developing NCDs.

Cholesterol is essential for the stability and architecture of the plasma membrane and a precursor of bile acids and steroid hormones in mammals. Excess dietary cholesterol uptake leads to hypercholesterolemia and atherosclerosis and plays a role in cancer development. The role of actin-binding scaffolding protein LIM and SH3 protein 1 (LASP1) in cholesterol trafficking has not been investigated previously. Cholesterol levels, its uptake, and excretion were studied in mice deficient for low-density lipoprotein receptor and Lasp1 (Ldlr-/-Lasp1-/- mice) upon feeding a high-fat diet, and in LASP1-knockdown, differentiated human intestinal epithelial CaCo-2 cells. When compared with diet-fed Ldlr-/- control mice, Ldlr-/-Lasp1-/- mice displayed a reduction in serum cholesterol levels. Mechanistically, we identified a new role of LASP1 in controlling the translocation of the intestinal cholesterol transporter Niemann-Pick C1-like 1 (NPC1L1) to the apical cell surface, which was limited in LASP1-knockdown human CaCo-2 enterocytes and in the intestine of Ldlr-/- Lasp1-/- compared with Ldlr-/- mice, linked to LASP1-pAKT signaling but not CDC42 activation. In line, a reduction in cholesterol reabsorption was noted in LASP1-knockdown CaCo-2 cells in vitro, and an enhanced cholesterol excretion via the feces was observed in Ldlr-/- Lasp1-/- mice. These data uncover a novel function of Lasp1 in cholesterol trafficking, promoting cholesterol reabsorption in the intestine. Targeting LASP1 locally could thus represent a novel targeting strategy to ameliorate hypercholesterolemia and associated diseases.NEW & NOTEWORTHY We here uncovered LASP1 as a novel regulator of the shuttling of the sterol transporter NPC1L1 to the cell surface in enterocytes to control cholesterol absorption. Accordingly, LASP1-deficient mice displayed lowered serum cholesterol levels under dietary cholesterol supplementation.

Epidemiological results on the link between chronic stress and cancer initiation have been inconsistent. This study examined the relation between chronic biological stress, indicated as hair cortisol (HairF) and hair cortisone (HairE), and cancer incidence, adjusting for metabolic syndrome (MetS) components. We analyzed HairF and HairE samples from 6341 participants from the population-based cohort Lifelines in 2014. A linkage with the Dutch Nationwide Pathology Databank (Palga) provided the cancer incidence from 2015 to 2021. The association between dichotomized HairF and log-transformed HairE (LogHairE) and cancer incidence was estimated using Cox regression. MetS components were evaluated as confounders or moderators. Of the 2776 participants with known HairF levels and no cancer history, 238 developed cancer. The HairF level did not predict cancer incidence (HR: 0.993, 95%CI: 0.740-1.333). No confounders or moderators were identified. Among the 4699 participants with known HairE levels and no cancer history, 408 developed cancer. There was no association between LogHairE and cancer incidence (HR: 1.113, 95%CI: 0.738-1.678). When including age as a confounder and gender as a moderator, LogHairE was statistically significantly associated with cancer incidence (HR: 6.403, 95%CI: 1.110-36.92). In a population-based cohort, chronic biological stress, measured by HairE, was associated with cancer incidence, after controlling for age and gender.

It remains unknown whether adiposity subtypes are differentially associated with colorectal cancer (CRC). To move beyond single-trait anthropometric indicators, we derived four multi-trait body shape phenotypes reflecting adiposity subtypes from principal components analysis on body mass index, height, weight, waist-to-hip ratio, and waist and hip circumference. A generally obese (PC1) and a tall, centrally obese (PC3) body shape were both positively associated with CRC risk in observational analyses in 329,828 UK Biobank participants (3728 cases). In genome-wide association studies in 460,198 UK Biobank participants, we identified 3414 genetic variants across four body shapes and Mendelian randomization analyses confirmed positive associations of PC1 and PC3 with CRC risk (52,775 cases/45,940 controls from GECCO/CORECT/CCFR). Brain tissue-specific genetic instruments, mapped to PC1 through enrichment analysis, were responsible for the relationship between PC1 and CRC, while the relationship between PC3 and CRC was predominantly driven by adipose tissue-specific genetic instruments. This study suggests distinct putative causal pathways between adiposity subtypes and CRC.

Changes in the local population are intricately linked to healthcare infrastructure, which subsequently impacts the healthcare sector. A decreasing local population can result in lagging health infrastructure, potentially leading to adverse health outcomes as patients may be at risk of not receiving optimal care and treatment. While some studies have explored the relationship between chronic diseases and local population decline, evidence regarding cancer is insufficient. In this study, we focused on how deteriorating management of chronic diseases such as dyslipidemia could influence the risk of cancer. We investigated the relationship between changes in the local population and cancer incidence among patients with dyslipidemia.

This cohort study was conducted using claims data. Data from adult patients with dyslipidemia from the National Health Insurance Service-National Sample Cohort conducted between 2002 and 2015 were included. Population changes in each region were obtained from the Korean Statistical Information Service and were used to link each individual's regional code. Cancer risk was the dependent variable, and Cox proportional hazards regression was used to estimate the target associations.

Data from 336,883 patients with dyslipidemia were analyzed. Individuals who resided in areas with a decreasing population had a higher risk of cancer than those living in areas with an increasing population (decrease: hazard ratio (HR) = 1.06, 95% CI = 1.03-1.10; normal: HR = 1.05, 95% CI = 1.02-1.09). Participants living in regions with a low number of hospitals had a higher risk of cancer than those in regions with a higher number of hospitals (HR = 1.20, 95% CI = 1.12-1.29).

Patients in regions where the population has declined are at a higher risk of cancer, highlighting the importance of managing medical problems caused by regional extinction. This could provide evidence for and useful insights into official policies on population decline and cancer risk.

Altered lipid metabolism is a hallmark of cancer development. However, the role of specific lipid metabolites in colorectal cancer development is uncertain.

In a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined associations between pre-diagnostic circulating concentrations of 97 lipid metabolites (acylcarnitines, glycerophospholipids and sphingolipids) and colorectal cancer risk. Circulating lipids were measured using targeted mass spectrometry in 1591 incident colorectal cancer cases (55% women) and 1591 matched controls. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between concentrations of individual lipid metabolites and metabolite patterns with colorectal cancer risk.

Of the 97 assayed lipids, 24 were inversely associated (nominally p < 0.05) with colorectal cancer risk. Hydroxysphingomyelin (SM (OH)) C22:2 (ORper doubling 0.60, 95% CI 0.47-0.77) and acylakyl-phosphatidylcholine (PC ae) C34:3 (ORper doubling 0.71, 95% CI 0.59-0.87) remained associated after multiple comparisons correction. These associations were unaltered after excluding the first 5 years of follow-up after blood collection and were consistent according to sex, age at diagnosis, BMI, and colorectal subsite. Two lipid patterns, one including 26 phosphatidylcholines and all sphingolipids, and another 30 phosphatidylcholines, were weakly inversely associated with colorectal cancer.

Elevated pre-diagnostic circulating levels of SM (OH) C22:2 and PC ae C34:3 and lipid patterns including phosphatidylcholines and sphingolipids were associated with lower colorectal cancer risk. This study may provide insight into potential links between specific lipids and colorectal cancer development. Additional prospective studies are needed to validate the observed associations.

World Cancer Research Fund (reference: 2013/1002); European Commission (FP7: BBMRI-LPC; reference: 313010).

Circulating metabolites systemically reflect cellular processes and can modulate the tissue microenvironment in complex ways, potentially impacting cancer initiation processes. Genetic background increases cancer risk in individuals with Lynch syndrome; however, not all carriers develop cancer. Various lifestyle factors can influence Lynch syndrome cancer risk, and lifestyle choices actively shape systemic metabolism, with circulating metabolites potentially serving as the mechanical link between lifestyle and cancer risk. This study aims to characterize the circulating metabolome of Lynch syndrome carriers, shedding light on the energy metabolism status in this cancer predisposition syndrome.This study consists of a three-group cross-sectional analysis to compare the circulating metabolome of cancer-free Lynch syndrome carriers, sporadic colorectal cancer (CRC) patients, and healthy non-carrier controls. We detected elevated levels of circulating cholesterol, lipids, and lipoproteins in LS carriers. Furthermore, we unveiled that Lynch syndrome carriers and CRC patients displayed similar alterations compared to healthy non-carriers in circulating amino acid and ketone body profiles. Overall, cancer-free Lynch syndrome carriers showed a unique circulating metabolome landscape.This study provides valuable insights into the systemic metabolic landscape of Lynch syndrome individuals. The findings hint at shared metabolic patterns between cancer-free Lynch syndrome carriers and CRC patients.

Recognizing the early signs of cancer risk is vital for informing prevention, early detection, and survival.

To investigate whether changes in circulating metabolites characterize the early stages of colorectal cancer (CRC) development, we examined the associations between a genetic risk score (GRS) associated with CRC liability (72 single-nucleotide polymorphisms) and 231 circulating metabolites measured by nuclear magnetic resonance spectroscopy in the Avon Longitudinal Study of Parents and Children (N = 6221). Linear regression models were applied to examine the associations between genetic liability to CRC and circulating metabolites measured in the same individuals at age 8 y, 16 y, 18 y, and 25 y.

The GRS for CRC was associated with up to 28% of the circulating metabolites at FDR-P < 0.05 across all time points, particularly with higher fatty acids and very-low- and low-density lipoprotein subclass lipids. Two-sample reverse Mendelian randomization (MR) analyses investigating CRC liability (52,775 cases, 45,940 controls) and metabolites measured in a random subset of UK Biobank participants (N = 118,466, median age 58 y) revealed broadly consistent effect estimates with the GRS analysis. In conventional (forward) MR analyses, genetically predicted polyunsaturated fatty acid concentrations were most strongly associated with higher CRC risk.

These analyses suggest that higher genetic liability to CRC can cause early alterations in systemic metabolism and suggest that fatty acids may play an important role in CRC development.

This work was supported by the Elizabeth Blackwell Institute for Health Research, University of Bristol, the Wellcome Trust, the Medical Research Council, Diabetes UK, the University of Bristol NIHR Biomedical Research Centre, and Cancer Research UK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This work used the computational facilities of the Advanced Computing Research Centre, University of Bristol - http://www.bristol.ac.uk/acrc/.

Resistin, a novel pro-inflammatory protein implicated in inflammatory processes, has been suggested to play a role in colorectal development. However, evidence from observational studies has been inconsistent. Mendelian randomization may be a complementary method to examine this association.

We conducted a two-sample Mendelian randomization to estimate the association between genetically determined circulating resistin concentrations and risk of colorectal cancer (CRC). Protein quantitative trait loci (pQTLs) from the SCALLOP consortium were used as instrumental variables (IVs) for resistin. CRC genetic summary data was obtained from GECCO/CORECT/CCFR (the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry), and FinnGen (Finland Biobank). The inverse variance weighted method (IVW) was applied in the main analysis, and other robust methods were used as sensitivity analyses. Estimates for the association from the two data sources were then pooled using a meta-analysis approach.

Thirteen pQTLs were identified as IVs explaining together 7.80% of interindividual variation in circulating resistin concentrations. Based on MR analyses, genetically determined circulating resistin concentrations were not associated with incident CRC (pooled-IVW-OR per standard deviation of resistin, 1.01; 95% CI 0.96, 1.06; p = 0.67. Restricting the analyses to using IVs within or proximal to the resistin-encoding gene (cis-IVs), or to IVs located elsewhere in the genome (trans-IVs) provided similar results. The association was not altered when stratified by sex or CRC subsites.

We found no evidence of a relationship between genetically determined circulating resistin concentrations and risk of CRC.

Cancer has become a leading cause of death among patients with metabolic syndrome (MetS). The more components of MetS a patient has, the higher his cancer risk is. MetS is causally associated with colorectal, pancreatic, gallbladder, biliary, hepatocellular, gastric and esophageal adenocarcinomas. MetS increases cancer mortality up to 2.4-fold. Intentional long-term weight loss reduces the excess cancer risk of obese MetS-patients. Preventing and treating the MetS together with GI cancer screening is effective and decreases the burden of GI cancer mortality significantly.

A fundamental understanding of the impact of bariatric surgery (BRS) on mechanisms of colorectal carcinogenesis is limited. For instance, studies report a reduced risk of colorectal cancer in females but not in males after BRS. We examined whether this sex-specific difference existed at the earlier polyp development stage.

This retrospective cohort study included 281,417 adults from the 2012-2020 MarketScan database. We compared polyps rates on colonoscopy in four groups: post- vs. pre-BRS (treatment) to post- vs. pre-severe obesity (SO) diagnosis (control). We focused our main analysis on a propensity-matched sample that yielded a balanced distribution of covariates in our four groups (n = 9680 adults, 21.9% males). We also adjusted for important covariates.

Metabolic syndrome parameters improved after bariatric surgery and worsened after severe obesity diagnosis (p < 0.05). The rate of polyps was 46.7% at a median of 0.5 years pre-BRS and 47.9% at a median of 0.6 years pre-SO diagnosis. The polyps rate was 45.4% at a median (range) of 3.2 (1.0-8.5) years post-BRS. Conversely, 53.8% of adults had polyps at 3.0 (1.0-8.6) years post-SO. There was no change in the risk of colorectal polyps in males or females post- vs. pre-BRS. However, the risk of polyps was higher in males (OR = 1.32, 95% CI: 1.02-1.70) and females (OR = 1.29, 95% CI: 1.13-1.47) post- vs. pre-SO. When compared to the control group (SO), the odds ratios for colorectal polyps were lower for males and females after bariatric surgery (OR = 0.63, 95% CI: 0.44-0.90, and OR = 0.79, 95% CI: 0.66-0.96, respectively).

Obesity is associated with an increased risk of colorectal polyps, an effect that is ameliorated after bariatric surgery. These data are relevant for studies investigating colorectal carcinogenesis mechanisms.

Cancer survival rates are increasing; however, studies on dyslipidemia as a comorbidity of cancer are limited. For efficient management of the disease burden, this study aimed to understand new-onset dyslipidemia in medically underserved areas (MUA) among cancer survivors > 19 years.

This study used 11-year (2009-2019) data from the Korean National Health Insurance Service sample cohort. Cancer survivors for five years or more (diagnosed with ICD-10 codes 'C00-C97') > 19 years were matched for sex, age, cancer type, and survival years using a 1:1 ratio with propensity scores. New-onset dyslipidemia outpatients based on MUA were analyzed using the Cox proportional hazards model.

Of the 5,736 cancer survivors included in the study, the number of new-onset dyslipidemia patients was 855 in MUA and 781 in non-MUA. Cancer survivors for five years or more from MUA had a 1.22-fold higher risk of onset of dyslipidemia (95% CI = 1.10-1.34) than patients from non-MUA. The prominent factors for the risk of dyslipidemia in MUA include women, age ≥ 80 years, high income, disability, complications, and fifth-year cancer survivors.

Cancer survivors for five years or more from MUA had a higher risk of new-onset dyslipidemia than those from non-MUA. Thus, cancer survivors for five years or more living in MUA require healthcare to prevent and alleviate dyslipidemia.

Hypercholesterolemia is often correlated with obesity which is considered a risk factor for various cancers. With the growing population of hypercholesterolemic individuals, there is a need to understand the role of increased circulatory cholesterol or dietary cholesterol intake towards cancer etiology and pathology. Recently, abnormality in the blood cholesterol level of colon cancer patients has been reported. In the present study, we demonstrate that alteration in cholesterol levels (through a high-cholesterol or high-fat diet) increases the incidence of chemical carcinogen-induced colon polyp occurrence and tumor progression in mice. At the cellular level, low-density lipoprotein cholesterol (LDLc) and high-density lipoprotein cholesterol (HDLc) promote colon cancer cell proliferation by tuning the cellular glucose and lipid metabolism. Mechanistically, supplementation of LDLc or HDLc promotes cellular glucose uptake, and utilization, thereby, causing an increase in lactate production by colon cancer cells. Moreover, LDLc or HDLc upregulates aerobic glycolysis, causing an increase in total ATP production through glycolysis, and a decrease in ATP generation by OXPHOS. Interestingly, the shift in the metabolic status towards a more glycolytic phenotype upon the availability of cholesterol supports rapid cell proliferation. Additionally, an alteration in the expression of the molecules involved in cholesterol uptake along with the increase in lipid and cholesterol accumulation was observed in cells supplemented with LDLc or HDLc. These results indicate that colon cancer cells directly utilize the cholesterol associated with LDLc or HDLc. Moreover, targeting glucose metabolism through LDH inhibitor (oxamate) drastically abrogates the cellular proliferation induced by LDLc or HDLc. Collectively, we illustrate the vital role of cholesterol in regulating the cellular glucose and lipid metabolism of cancer cells and its direct effect on the colon tumorigenesis.

Compelling pieces of epidemiological, clinical, and experimental research have demonstrated that Diabetes mellitus (DM) is a major risk factor associated with increased cancer incidence and mortality in many human neoplasms. In the pathophysiology context of DM, many of the main classical actors are relevant elements that can fuel the different steps of the carcinogenesis process. Hyperglycemia, hyperinsulinemia, metabolic inflammation, and dyslipidemia are among the classic contributors to this association. Furthermore, new emerging actors have received particular attention in the last few years, and compelling data support that the microbiome, the epigenetic changes, the reticulum endoplasmic stress, and the increased glycolytic influx also play important roles in promoting the development of many cancer types. The arsenal of glucose-lowering therapeutic agents used for treating diabetes is wide and diverse, and a growing body of data raised during the last two decades has tried to clarify the contribution of therapeutic agents to this association. However, this research area remains controversial, because some anti-diabetic drugs are now considered as either promotors or protecting elements. In the present review, we intend to highlight the compelling epidemiological shreds of evidence that support this association, as well as the mechanistic contributions of many of these potential pathological mechanisms, some controversial points as well as future challenges.

Diffuse large B-cell lymphoma (DLBCL) is a kind of highly heterogeneous non-Hodgkin lymphoma, both in clinical and genetic terms. DLBCL is admittedly categorized into six subtypes by genetics, which contain MCD, BN2, EZB, N1, ST2, and A53. Dyslipidemia is relevant to a multitude of solid tumors and has recently been reported to be associated with hematologic malignancies. We aim to present a retrospective study investigating dyslipidemia in DLBCL based on the molecular subtypes.

This study concluded that 259 patients with newly diagnosed DLBCL and their biopsy specimens were available for molecular typing. Results show that the incidence of dyslipidemia (87.0%, p <0.001) is higher in the EZB subtype than in others, especially hypertriglyceridemia (78.3%, p = 0.001) in the EZB subtype. Based on the pathological gene-sequencing, patients with BCL2 gene fusion mutation are significantly correlative with hyperlipidemia (76.5%, p = 0.006) and hypertriglyceridemia (88.2%, p = 0.002). Nevertheless, the occurrence of dyslipidemia has no remarkable influence on prognosis.

In summary, dyslipidemia correlates with genetic heterogeneity in DLBCL without having a significant influence on survival. This research first connects lipids and genetic subtypes in DLBCL.

Patients with prior colorectal polyps are at high risk for metachronous colorectal neoplasia, especially in the presence of obesity. We assessed the impact of 2 common bariatric surgeries, vertical sleeve gastrectomy and roux-n-Y gastric bypass, on the risk of colorectal neoplasia recurrence. This nationally representative analysis included 1183 postbariatric adults and 3193 propensity score-matched controls, who all had prior colonoscopy with polyps and polypectomy. Colorectal polyps reoccurred in 63.8% of bariatric surgery patients and 71.7% of controls at a mean follow-up of 53.1 months from prior colonoscopy. There was a reduced odds of colorectal polyp recurrence after bariatric surgery compared with controls (odds ratio [OR] = 0.70, 95% confidence interval [CI] = 0.58 to 0.83). This effect was most pronounced in men (OR = 0.58, 95% CI = 0.42 to 0.79), and post roux-n-Y gastric bypass (OR = 0.57, 95% CI = 0.41 to 0.79). However, the risk of rectal polyps or colorectal cancer remained consistent between groups. This study is the first to our knowledge to show a reduction in risk of polyp recurrence following bariatric surgery.

Chronic kidney disease (CKD) is associated with malignancy, including colorectal cancer, via the potential mechanism of chronic inflammation status. This study aimed to determine whether influenza vaccines can reduce the risk of colorectal cancer in patients with CKD. Our cohort study enrolled 12,985 patients older than 55 years with a diagnosis of CKD in Taiwan from the National Health Insurance Research Database at any time from 1 January 2001 to 31 December 2012. Patients enrolled in the study were divided into a vaccinated and an unvaccinated group. In this study, 7490 and 5495 patients were unvaccinated and vaccinated, respectively. A propensity score was utilized to reduce bias and adjust the results. Cox proportional hazards regression was used to estimate the correlation between the influenza vaccine and colorectal cancer in patients with CKD. The results showed that the influenza vaccine exerted a protective effect against colorectal cancer in populations with CKD. The incidence rate of colon cancer in the vaccinated group was significantly lower than in the unvaccinated group, with an adjusted hazard rate (HR) of 0.38 (95% CI: 0.30-0.48, p < 0.05). After the propensity score was adjusted for Charlson comorbidity index, age, sex, dyslipidemia, hypertension, diabetes, monthly income, and level of urbanization, the dose-dependent effect was found, and it revealed adjusted HRs of 0.74 (95% CI: 0.54-1.00, p < 0.05), 0.41 (95% CI: 0.30-0.57, p < 0.001), 0.16 (95% CI: 0.11-0.25, p < 0.001) for one, two to three, and four or more vaccinations, respectively. In summary, the influenza vaccine was found to be associated with a reduced risk of colorectal cancer in CKD patients. This study highlights the potential chemopreventive effect of influenza vaccination among patients with CKD. Future studies are required to determine whether the aforementioned relationship is a causal one.

Colorectal cancer (CRC) ranks third among fatal diseases afflicting mankind globally due to the shortage of primary detection methods and appropriate choice of drugs. Moreover, current treatments such as chemo drugs and radiotherapies create adverse effects and lead to drug resistance. In this context, recent advances in nanomedicine offer novel clinical solutions for colon cancer therapy. The current study denotes the therapeutic roles of biogenic Abutilon indicum silver and gold nanoparticles (AIAgNPs and AIAuNPs) against a 1, 2-dimethyl hydrazine (DMH)-induced CRC in Wistar rats. Following treatment of nanoparticles (NPs), the CRC rats showed great localization of AIAgNPs and AIAuNPs in colon tumors shown by ICP-OES, indicating their bioavailability. The AIAgNPs and AIAuNPs significantly enhanced cellular antioxidant enzyme levels including catalase, SOD, GSH, GPx and reduced lipid peroxidation (LPO) compared to the standard drug paclitaxel. AIAgNPs and AIAuNPs revealed significant protection against metastasis compared to paclitaxel shown in the histopathological study. The important CRC signaling molecules of the Wnt pathway, the β-catenin and Tcf-4 levels were significantly downregulated in AIAgNPs and AIAuNPs treated CRC rats compared to paclitaxel. Furthermore, the expression levels of cleaved apoptotic caspase-9, -8, and - 3 and lamins were significantly upregulated in AIAgNPs and AIAuNPs treated CRC rats compared to paclitaxel. This preclinical study provides substantial insights into the anti-colon cancer roles of biogenic NPs and gives an idea for targeting different cancers.

Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide. Although most prevalent among older people, its incidence above 50 years old has been decreasing globally in the last decades, probably as a result of better screening. Paradoxically, its incidence in patients below 50 years old [early-onset CRC (EO-CRC)] has been increasing, for reasons not yet fully understood. EO-CRC's increasing incidence is genre independent but shows racial disparities and has been described to occur worldwide. It follows a birth-cohort effect which probably reflects a change in exposure to CRC risk factors. Its incidence is predicted to double until 2030, which makes EO-CRC a serious public health issue. Both modifiable and non-modifiable risk factors have been identified - some are potential targets for preventive measures. EO-CRC is often diagnosed at advanced stages and histological features associated with poor prognosis have been described. EO-CRC presents some distinctive features: Microsatellite in-stability is common, but another subtype of tumours, both microsatellite and chromosome stable also seems relevant. There are no age-specific treatment protocols and studies on EO-CRC survival rates have shown conflicting data. Due to the higher germline pathological mutations found in EO-CRC patients, an accurate genetic risk evaluation should be performed. In this review, we summarize the current evidence on epidemiological, clinical, histopathological and molecular features of EO-CRC and discuss the contribution of genetics and lifestyle risk factors. We further comment on screening strategies and specific dimensions to consider when dealing with a younger cancer patient.

Metabolic syndrome (MetS), a group of risk factors that define metabolic dysfunction in adults, is strongly associated with obesity and is an emerging risk factor for cancer. However, the association of MetS and degree of metabolic dysfunction with obesity-related cancer is unknown.

Using National Health and Nutrition Examination Survey data from 1999 to 2018, we identified 528 obesity-related cancer cases and 18,972 cancer-free participants. MetS was defined as the presence of or treatment for ≥3 of hyperglycemia, hypertension, hypertriglyceridemia, low HDL-cholesterol, and abdominal obesity. A metabolic syndrome score (MSS) was computed as the total number of abnormal MetS parameters to determine the severity of metabolic dysfunction. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression models, adjusting for sociodemographic and lifestyle factors.

About 45.7% of obesity-related cancer cases were classified as having MetS compared with only 33.0% of cancer-free participants. Overall, MetS and MSS were not associated with obesity-related cancer. However, MSS was associated with higher obesity-related cancer risk among participants under 50 years of age (OR [95% CI] = 1.28 [1.08-1.52]). When evaluating MSS categorically, compared with healthy participants with no abnormal MetS parameters (MSS = 0), participants with one or two abnormal parameters had a statistically significant higher risk of obesity-related cancer (OR [95% CI] = 1.73 [1.06-2.83]).

Metabolic dysfunction is associated with a higher risk of obesity-related cancer, particularly in young adults under 50 years of age, and among participants with one or two abnormal metabolic parameters. A more accurate indicator of metabolic dysfunction, beyond metabolic syndrome, is needed to better assist in stratifying individuals for obesity-related cancer risk.

The associations between blood lipids, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides, and low-density lipoprotein cholesterol (LDL-C), and colorectal cancer risk are controversial. We evaluated potential causal relationships between blood lipids and colorectal cancer risk. Using the baseline data from the Japanese Consortium of Genetic Epidemiology studies, we estimated the single-nucleotide polymorphism (SNP)-exposure associations (n = 34,546 for TC, n = 50,290 for HDL-C, n = 51,307 for triglycerides, and n = 30,305 for LDL-C). We also estimated the SNP-outcome associations in another Japanese dataset (n = 7,936 colorectal cancer cases and n = 38,042 controls). We conducted Mendelian randomization (MR) analyses for the association between each blood lipid type and the risk of colorectal cancer using an inverse variance-weighted method. The total variances explained by the selected SNPs in TC (68 SNPs), HDL-C (50 SNPs), log-transformed triglycerides (26 SNPs), and LDL-C (35 SNPs) were 7.0%, 10.0%, 6.2%, and 5.7%, respectively. The odds ratios for colorectal cancer were 1.15 [95% confidence interval (CI), 1.01-1.32] per 1 standard deviation (SD; 33.3 mg/dL) increase in TC, 1.11 (95% CI, 0.98-1.26) per 1 SD (15.4 mg/dL) increase in HDL-C, 1.06 (95% CI, 0.90-1.26) per 1 SD (0.5 log-mg/dL) increase in log-transformed triglycerides, and 1.17 (95% CI, 0.91-1.50) per 1 SD (29.6 mg/dL) increase in LDL-C. Sensitivity analyses consistently suggested the positive association between TC and colorectal cancer, whereas results of each lipid component were inconsistent. In conclusion, this large MR study of a Japanese population showed a potentially causal association between high TC and colorectal cancer risk, although the association between each lipid component and colorectal cancer remained inconclusive.

In this large MR analysis of a Japanese population, a positive association was found between genetically predicted high total cholesterol (TC) levels and an increased risk of colorectal cancer. Therefore, lowering TC levels by lifestyle modifications or medications may be justified for the purpose of preventing colorectal cancer.

The concentration of serum ferritin, a storage form of iron, may be associated with carcinogenesis in various cancers. There are only limited studies on the relationship between serum ferritin levels and colorectal cancer (CRC) risk, especially in the Asian population. This study aimed to analyze the association between CRC incidence and serum ferritin levels.

This was a national cohort study that used health checkup and insurance claims data of the Korean population. CRC incidence according to the serum ferritin level was analyzed during 2008-2018 in 17,116 participants.

The hazard ratio (HR) of CRC incidence decreased as serum ferritin levels increased (Q1: HR, 1.000 [95% confidence interval [CI], reference]; Q2: HR, 0.811 [95% CI, 0.558 to 1.178]; Q3: HR, 0.654 [95% CI, 0.442 to 0.968]; Q4: HR, 0.443 [95% CI, 0.285 to 0.687]; p = 0.0026). In subgroup analysis, 40 to 64 years of age, sex, body mass index of &lt; 25 kg/ m2, presence of metabolic syndrome, absence of diabetes mellitus, and absence of anemia had HRs of &lt; 0.5 (95% CI) in the highest quartiles compared with that in the lowest quartiles.

This study shows an inverse association between serum ferritin and CRC risk. Serum ferritin measurement can aid in identifying young adults requiring active CRC screening.

Dyslipidemia has been associated with cancer risk, yet the relationship between lipid ratios and nonsmall-cell lung cancer (NSCLC) is still unclear. This study aimed to explore the value of lipid ratios, including total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) and triglyceride/HDL-C (TG/HDL-C) as predictors of NSCLC in a Chinese population. Adult patients with histologically confirmed NSCLC, without a previous history of cancer, concomitant disease associated with lipid metabolism disorders, or usage of lipid-lowering drugs, were enrolled from a single center. Controls without NSCLC, matched for age and sex, were enrolled from the same Center. Lipid profile including TC, TG, HDL-C were measured in all participants. TC/HDL-C and TG/HDL-C were calculated based on the levels of TC, TG, HDL-C. Seven hundred eighty-two NSCLC cases and 599 controls were enrolled. NSCLC patients had significantly higher TG/HDL-C and TC/HDL-C levels than those in the control. After controlling for confounding factors, TG/HDL-C (OR = 4.489, 95% CI: 2.463-6.035, P < .001) and TC/HDL-C (OR = 2.396, 95% CI: 2.086-2.752, P = .001) were independently associated with NSCLC risk. The incidence of NSCLC was increased with rising tertiles of TG/HDL-C and TC/HDL-C. Moreover, patients with TNM II-IV stage NSCLC had higher TG/HDL-C and TC/HDL-C than those in TNM I and Tis stage. TG/HDL-C and TC/HDL-C are positively correlated with NSCLC risk and TG/HDL-C is more predictive than TC/HDL-C in predicting the risk of NSCLC. The highest AUC was that of TG/HDL (0.898), at a cutoff point of 0.62, with 83.6% sensitivity and 83.5% specificity.