Increased Risk Of Colorectal Cancer Research Articles

Impact of Chondroitin Sulfate Proteoglycan 4 Pseudogene 12 Genetic Variants on Colorectal Cancer Risk: A Case-Control Study.

This study aims to investigate the correlation between the chondroitin sulfate proteoglycan 4 pseudogene 12 (CSPG4P12) polymorphism and the risk of colorectal cancer (CRC). This case-control study involved 850 patients with CRC and 850 health controls. The genotypes of CSPG4P12 (rs2880765, rs6496932, and rs8040855) were determined by the TaqMan-MGB probe method. Logistic regression model was employed to evaluate the association of CSPG4P12 single-nucleotide polymorphisms (SNPs) with the risk of CRC by calculating the odds ratio (OR) and 95% confidence interval (CI). The CSPG4P12 exhibited lower expression in CRC tissues. Our data showed that the rs6496932 variant increased CRC risk (CA vs. CC: p = 0.006; CA + AA vs. CC: p = 0.005). In contrast, the rs8040855 variant reduced the risk of CRC (CG vs. CC: p < 0.001; CG + GG vs. CC: p < 0.001). Stratification by gender and age revealed that the rs8040855 variant decreased CRC risk; however, the rs6496932 variant increased CRC risk among males (CA vs. CC: p = 0.024; CA + AA vs. CC: p = 0.014) and younger individuals (CA vs. CC: p = 0.004; CA + AA vs. CC: p = 0.010). When stratified by smoking and drinking status, the rs8040855 variant decreased CRC risk among nonsmokers (CG vs. CC: p < 0.001; CG + GG vs. CC: p < 0.001) and nondrinkers (CA vs. CC: p = 0.002; CA + AA vs. CC: p = 0.004). The rs6496932 variant increased CRC risk among nonsmokers (CA vs. CC: p = 0.016; CA + AA vs. CC: p = 0.036) and nondrinkers (CG vs. CC: p < 0.001; CG + GG vs. CC: p < 0.001). Haplotype analysis showed that the CSPG4P12 Trs2880765Crs6496932Grs8040855 haplotype reduced the risk of CRC compared with the reference haplotype (CSPG4P12 Ars2880765Crs6496932Crs8040855) (OR = 0.46, 95% CI = 0.26-0.82, p = 0.049). These findings highlight the potential of these genetic variants as biomarkers for CRC susceptibility, offering insights into personalized prevention strategies.

Colorectal cancer and associated genetic, lifestyle, cigarette, nargileh-hookah use and alcohol consumption risk factors: a comprehensive case-control study.

This study aimed to investigate the causes and risk factors of colorectal cancer (CRC) in a Turkish population, focusing on various modifiable and non-modifiable risk factors. A hospital-based case-control design was employed to compare individuals with CRC (cases) to individuals without CRC (controls). Male and female participants were recruited from the surgery, internal medicine, and out-patient departments. The study encompassed socio-demographic data, clinical information, radiological diagnoses, and biochemical measurements. Univariable and multivariable logistic regressions were used to determine associated risk factors of CRC. The study included 704 individuals with CRC and 704 controls. Significant socio-demographic disparities were observed between the groups, with over 30% of the cases having lower levels of education and income compared to the controls. Lifestyle factors such as obesity, higher rates of smoking (cigarettes and hookah) and alcohol consumption were more prevalent among cases than controls. Further significant associations were identified with intestinal inflammation, obesity, processed food consumption, and symptoms such as abdominal pain, cramps, diarrhea, constipation, blood in stool, bloating, irritable bowel syndrome, nausea/vomiting, anemia, stress, fatigue, weakness, and weight loss. Diet analysis revealed that individuals with CRC consumed more red meat, processed and fast foods along with less pulses and vegetables. Genetic predispositions and exposure to chemicals also correlated strongly with increased CRC risk. Multivariable regression analysis identified, nausea/vomiting, constipation, intestinal disease, genetics factor, hookah-nargileh use, history of any cancer, family history of bowel cancer, constipation, cigarette smoking, stress, milk-yogurt consumption, obesity and red meat consumption as significant determinants for CRC. CRC risk is influenced by dietary, lifestyle, and genetic factors. Awareness of hereditary risk and participation in screening are crucial. Lifestyle changes, such as avoiding smoking, hookah, and alcohol use, and adopting a healthy diet, are essential for prevention.

Gene-environment interactions and colorectal cancer risk: A case-control study on xenobiotic metabolizing enzyme polymorphisms in the Jammu& Kashmir, India population

BackgroundCancer remains a significant global health concern, with colorectal cancer (CRC) showing a rising incidence, particularly among younger populations. Most CRC cases are linked to a complex interplay of genetic and environmental factors. The cytochrome P450 (CYP) superfamily, including enzymes like CYP2A13 and CYP2A6, plays a vital role in metabolizing environmental carcinogens such as polycyclic aromatic hydrocarbons (PAHs) and nitrosamines. Polymorphisms in these genes, alongside phase II glutathione-S-transferases (GSTs) involved in detoxification, can influence individual cancer risk. This study focuses on the association between these genetic polymorphisms and CRC risk in the Jammu & Kashmir, population, a region with high exposure to dietary and lifestyle-related carcinogens. MethodologyThis hospital-based case-control study was conducted at the Sher-I-Kashmir Institute of Medical Sciences (SKIMS), Srinagar, J&K, India between March 2019 and March 2022. The study included 246 histopathologically confirmed colorectal cancer (CRC) cases, and an equal number of matched controls based on age (±5 years), gender, and place of residence. Blood samples were collected for DNA extraction, followed by genotyping of xenobiotic-metabolizing enzyme (XME) genes, including CYP2A13, CYP2A6, and GSTs using standard PCR-RFLP and multiplex PCR methods. Statistical analyses were performed using STATA software to assess the association between gene polymorphisms and CRC risk. ResultsThe study revealed key associations between genetic and environmental factors and CRC risk. The analysis demonstrated that cases had significantly lower education levels than controls. Family history of cancer, smoking, and dietary factors like red meat and salt tea consumption were more prevalent among cases. Genetic analysis identified significant interactions between various CYP and GST genotypes, and environmental factors such as smoking, pesticide exposure, and diet, with varying effects on CRC risk. ConclusionThe research underscores the influence of genetic and environmental factors on colorectal cancer (CRC) risk. Lower educational was associated with a heightened risk of CRC. Certain genotype variants of xenobiotic metabolizing enzymes (XME) were found to increase CRC risk, particularly in conjunction with smoking, pesticide exposure, and sun-dried vegetable consumption. A family history of cancer, especially CRC, further amplified the risk. These findings emphasize the importance of developing personalized CRC prevention and screening strategies that account for gene-environment interactions.

Risk of Colorectal Cancer among Patients with One or Multiple Metabolic Syndrome Components

Background/Objectives: Dysfunctions of metabolic syndrome (MetS) have been identified as a significant risk factor for colorectal cancer (CRC). However, current colon cancer guidelines do not classify patients with MetS as high risk, thereby leaving these individuals vulnerable. Consequently, we explored the relationship between MetS, its individual components, and the development of CRC in a cohort of patients with MetS to assess the necessity for CRC screening in these individuals. Methods: This study included patients ages 18 and older that received a service from the Marshall-Health (MH) practice plan, Cabell-Huntington Hospital (CHH), MU/JCESOM’s Edwards Comprehensive Cancer Center (ECCC), or the University of Kentucky HealthCare (UKHC) system between 2010 and 2018. We implemented log-binomial regression models to assess the individual and collective effects of MetS components after adjusting other CRC risk factors. Results: Given that CRC prevalence increases in the older population (aged 65 years and above), and that multiple components of MetS are observed within the same population, we analyzed the concurrent impact of all MetS components on CRC. Log-binomial regression models were implemented to assess the risk of CRC due to MetS components after adjusting other risk factors. Conclusions: We identified specific components that markedly increased CRC risk, suggesting that individuals with these components should be prioritized for early screening. These findings could significantly influence early CRC screening protocols, with the ultimate aim to reduce mortality associated with the disease.

Predicting the risk of colorectal cancer among diabetes patients using a random survival forest-guided approach.

Colorectal cancer (CRC) is the third most frequently diagnosed cancer worldwide. Diabetes and CRC share many overlapping lifestyle risk factors such as obesity, heavy alcohol use, and diet. This study aims to develop a risk scoring system for CRC prediction among diabetes patients using routine medical records. A retrospective cohort study was conducted using electronic health records of Hong Kong. Patients who received diabetes care in public general outpatient clinics between 2010 and 2019 and had no cancer history were identified, and followed up until December 2019. The outcome was diagnosis of CRC during follow-up. For model building, predictors were first selected using random survival forest, and weights were subsequently assigned to selected predictors using Cox regression. Of the 386,325 patients identified, 4,199 patients developed CRC during a median follow-up of 6.2 years. The overall incidence rate of CRC was 1.93 per 1000 person-years. In the final scoring system, age, waist-to-hip ratio, and serum creatinine were included as predictors. The C-index on test set was 0.651 (95%CI: 0.631-0.669). Elevated serum creatinine (≥127 µmol/L) could be a potential important predictor of increased CRC risk. While obesity is a well-known risk factor for CRC, renal dysfunction could be potentially linked to an elevated risk of CRC among diabetes patients. Further studies are warranted to explore whether renal function could be a potential parameter to guide screening recommendation for diabetes patients.

Genetic Variation and Regulation of MICA Alters Natural Killer Cell-Mediated Immunosurveillance in Early-Onset Colorectal Cancer.

The incidence of colorectal cancer (CRC) among individuals under age 50, or early-onset CRC (EOCRC), has been rising over the past few decades for unclear reasons, and the etiology of the disease remains largely unknown. Known genetic risk factors do not explain this increase, pointing to possible environmental and as-yet unidentified genetic contributors and their interactions. Previous research linked genetic variation on chromosome 6 to increased CRC risk. This region harbors multiple immune genes, including the gene encoding Major Histocompatibility Complex (MHC) class I polypeptide-related sequence A (MICA). MICA is a polygenic ligand for the Natural Killer Group 2D receptor (NKG2D), a receptor expressed on Natural Killer (NK) cells and other lymphocytes. Given that intra-tumoral NK cell infiltration correlates with favorable CRC outcomes, we hypothesized that germline genetic variation in MICA could influence CRC risk. In a discovery set of 40,125 cases and controls, we show that the minor G allele at Chr6:31373718C>G (hg19) is associated with increased risk for CRC (odds ratio (OR) = 1.09, 95% confidence interval (CI) 1.04 - 1.15, p = 0.0009). The effect is stronger in EOCRC (OR = 1.26, 95% CI 1.08 - 1.44, p = 0.0023) than in those 50 and over (OR = 1.07, 95% CI 1.02 - 1.13; p = 0.012) (Ratio of ORs = 1.32, 95% CI 1.14 - 1.52, p = 0.0002). In an independent validation set of 77,983 cases and controls, the adjusted interaction by age-of-onset was significant at OR = 1.15 (95% CI 1.03 - 1.34, p = 0.0150) with a higher risk in EOCRC. Expression quantitative trait locus analysis in normal colonic epithelia showed that MICA RNA expression decreases linearly with each additional copy of the minor G allele (p = 3.345 × 10e-18). Bulk RNA analysis of the tumor immune microenvironment revealed that tumors from patients with CG or GG genotypes have lower resting and activated NK cell infiltration as compared to tumors from patients with CC genotype. Multiplex immunofluorescence analysis demonstrated that patients with a G allele (i.e. CG or GG genotype, but not CC genotype) have a statistically significant decrease in the number of NK cells in tumor compared to adjacent normal colonic mucosa. Taken together, population-based epidemiologic, molecular, genetic, cellular and immunologic evidence demonstrate that MICA genotype is associated with increased risk of EOCRC and reduced number of NK cells in colorectal tumors, suggesting that patients with a G allele have altered NK cell-mediated immunosurveillance. These novel findings suggest that EOCRC may have a previously unrecognized innate immune-mediated etiology which merits further investigation.

Revealing the association between East Asian oral microbiome and colorectal cancer through Mendelian randomization and multi-omics analysis.

Colorectal cancer (CRC) poses a global health threat, with the oral microbiome increasingly implicated in its pathogenesis. This study leverages Mendelian Randomization (MR) to explore causal links between oral microbiota and CRC using data from the China National GeneBank and Biobank Japan. By integrating multi-omics approaches, we aim to uncover mechanisms by which the microbiome influences cellular metabolism and cancer development. We analyzed microbiome profiles from 2017 tongue and 1915 saliva samples, and GWAS data for 6692 CRC cases and 27178 controls. Significant bacterial taxa were identified via MR analysis. Single-cell RNA sequencing and enrichment analyses elucidated underlying pathways, and drug predictions identified potential therapeutics. MR identified 19 bacterial taxa significantly associated with CRC. Protective effects were observed in taxa like RUG343 and Streptococcus_umgs_2425, while HOT-345_umgs_976 and W5053_sp000467935_mgs_712 increased CRC risk. Single-cell RNA sequencing revealed key pathways, including JAK-STAT signaling and tyrosine metabolism. Drug prediction highlighted potential therapeutics like Menadione Sodium Bisulfite and Raloxifene. This study establishes the critical role of the oral microbiome in colorectal cancer development, identifying specific microbial taxa linked to CRC risk. Single-cell RNA sequencing and drug prediction analyses further elucidate key pathways and potential therapeutics, providing novel insights and personalized treatment strategies for CRC.

Allostatic Load, Genetic Susceptibility, Incidence Risk, and All-cause Mortality of Colorectal Cancer.

Allostatic load (AL) reflects the cumulative burden of chronic stress throughout life, potentially influencing the onset and prognosis of cancer. However, the associations between AL, colorectal cancer (CRC) risk and all-cause mortality in patients with CRC remain unclear. We analyzed the association between AL and CRC risk in 304,959 adults and all-cause mortality in 1,794 patients with CRC from the UK Biobank, using Cox proportional hazards regression models. Compared to the AL level in the first quartile, individuals in the second to fourth quartiles had a respective 20%, 29%, and 43% increased risk of CRC; 15%, 24%, and 42% increased risk for colon cancer; and 30%, 38%, and 45% increased risk for rectal cancer. We identified a positive dose-gradient association of AL score with CRC risk, including colon and rectal cancer. Additionally, the association between AL and increased risk of CRC was observed across different strata of genetic susceptibility for CRC. Eliminating AL exposures could prevent nearly 39.24% (95% CI: 36.16-42.32) of CRC incident cases. Meanwhile, a significant association between the AL and all-cause mortality in patients with CRC was found, with a HR of 1.71 (95% CI: 1.16-2.50) for the fourth quartile compared to the AL score in the first quartile, demonstrating a positive dose-response relationship. High AL was associated with increased CRC risk and all-cause mortality in CRC patients. Future research should prioritize the development of cognitive or behavioral intervention strategies to mitigate the adverse effects of AL on CRC incidence and prognosis.

Impact of Ascending HPV Infection on Colorectal Cancer Risk: Evidence from a Nationwide Study.

Colorectal cancer (CRC) is a prevalent and escalating health issue in Taiwan. This nationwide study delves into the relationship between Human Papillomavirus (HPV) infection and CRC risk, employing population datasets from 2007 to 2017. Cox regression analyses revealed a statistically significant hazard ratio (HR) of 1.73 (95% CI: 1.63-1.83) for CRC in HPV-positive patients, indicating a considerably elevated risk compared to non-infected individuals. Further, stratification by sex showed males with HPV have a higher CRC risk (HR = 1.49, 95% CI: 1.40-1.58) compared to females. Age-related analysis uncovered a progressive increase in CRC risk with advancing age (HR = 34.69 for over 80 years). The study of specific CRC subtypes showed varying risks: HR = 1.74 for the colon, HR = 1.64 for the rectum, and a notably higher HR = 4.72 for the anus. Comorbid conditions such as hypertension (HR = 1.26), diabetes mellitus (HR = 1.32), and abnormal liver function (HR = 1.18) also correlate with significantly increased CRC risks. These findings suggest that HPV is a significant risk factor for CRC, with disparities in risk based on anatomical location, demographic characteristics, and comorbidities, highlighting the need for intervention strategies and targeted prevention.

An Empirical Dietary Pattern Associated With the Gut Microbial Features in Relation to Colorectal Cancer Risk

Background & AimsEpidemiologic evidence for dietary influence on colorectal cancer (CRC) risk through the gut microbiome remains limited. MethodsLeveraging 307 men and 212 women with stool metagenomes and dietary data, we characterized and validated a sex-specific dietary pattern associated with the CRC-related gut microbial signature (CRC Microbial Dietary Score [CMDS]). We evaluated the associations of CMDS with CRC risk according to Fusobacterium nucleatum, pks+Escherichia coli, and enterotoxigenic Bacteroides fragilis (ETBF) status in tumor tissue using Cox proportional hazards regression in the Health Professionals Follow-up Study (1986-2018), Nurses’ Health Study (NHS) (1984-2020), and NHS II (1991-2019). ResultsThe CMDS was characterized by high industrially processed foods and low unprocessed fiber-rich foods intakes. In 259,200 participants, we documented 3,854 incident CRC cases over 6,467,378 person-years of follow-up. CMDS was associated with a higher risk of CRC (Ptrend<0.001), with a multivariable hazard ratio (HRQ5vs.Q1) of 1.25 (95%CI, 1.13-1.39). The association remained after adjusting for previously established dietary patterns, e.g., the Western and prudent diets. Notably, the association was stronger for tumoral F. nucleatum-positive (HRQ5vs.Q1, 2.51; 95%CI, 1.68-3.75; Ptrend<0.001) (Pheterogeneity=0.03, positivity vs. negativity), pks+E. coli-positive (HRQ5vs.Q1, 1.68; 95%CI, 0.84-3.38; Ptrend=0.005) (Pheterogeneity=0.01, positivity vs. negativity), and ETBF-positive CRC (HRQ5vs.Q1, 2.06; 95%CI, 1.10-3.88; Ptrend=0.016) (Pheterogeneity=0.06, positivity vs. negativity), compared with their negative counterparts. ConclusionsCMDS was associated with increased CRC risk, especially for tumors with detectable F. nucleatum, pks+E. coli, and ETBF in tissue. Our findings support a potential role of the gut microbiome underlying the dietary effects on CRC.

Understanding Lifestyle Choices That Increase Colorectal Cancer Risk

Understanding Lifestyle Choices That Increase Colorectal Cancer Risk

Colorectal cancer prognosis based on dietary pattern using synthetic minority oversampling technique with K-nearest neighbors approach

Generally, a person’s life span depends on their food consumption because it may cause deadly diseases like colorectal cancer (CRC). In 2020, colorectal cancer accounted for one million fatalities globally, representing 10% of all cancer casualties. 76,679 males and 78,213 females over the age of 59 from ten states in the United States participated in this analysis. During follow-up, 1378 men and 981 women were diagnosed with colon cancer. This prospective cohort study used 231 food items and their variants as input features to identify CRC patients. Before labelling any foods as colorectal cancer-causing foods, it is ethical to analyse facts like how many grams of food should be consumed daily and how many times a week. This research examines five classification algorithms on real-time datasets: K-Nearest Neighbour (KNN), Decision Tree (DT), Random Forest (RF), Logistic Regression with Classifier Chain (LRCC), and Logistic Regression with Label Powerset (LRLC). Then, the SMOTE algorithm is applied to deal with and identify imbalances in the data. Our study shows that eating more than 10 g/d of low-fat butter in bread (RR 1.99, CI 0.91–4.39) and more than twice a week (RR 1.49, CI 0.93–2.38) increases CRC risk. Concerning beef, eating in excess of 74 g of beef steak daily (RR 0.88, CI 0.50–1.55) and having it more than once a week (RR 0.88, CI 0.62–1.23) decreases the risk of CRC, respectively. While eating beef and dairy products in a daily diet should be cautious about quantity. Consuming those items in moderation on a regular basis will protect us against CRC risk. Meanwhile, a high intake of poultry (RR 0.2, CI 0.05–0.81), fish (RR 0.82, CI 0.31–2.16), and pork (RR 0.67, CI 0.17–2.65) consumption negatively correlates to CRC hazards.

Impact of processed and ultra-processed foods on colorectal cancer risk: Mechanisms, dietary factors, and protective compound

Colorectal cancer (CRC) is the third most common malignant neoplasm worldwide, linked to behavioral factors such as a sedentary lifestyle and smoking, environmental factors like pollution, and nutritional factors including a diet rich in red and processed meats. Some foods are associated with potential carcinogenicity, while others act as protective factors. This review aims to report the contribution of processed and ultra-processed foods to the etiopathogenesis of CRC and explore the role of protective diets. The article is an integrative review conducted in PubMed and VHL databases using the descriptors “colorectal cancer” and “processed foods.” Studies published in the last five years addressing the relationship between these foods and CRC development were included. Potentially carcinogenic substances in processed foods, such as heterocyclic amines, nitrosamines, heme iron, industrial fatty acids, aromatic hydrocarbons, sialic acid sugar, and additives like titanium dioxide, were associated with colon and rectal neoplasms. Additional associations were found with the human microbiome, packaging materials, and food preparation methods. Conversely, several food components can protect against CRC. The consumption of processed and ultra-processed foods can significantly increase CRC risk through mechanisms like inflammation, oxidative stress, gene expression changes, and genetic material damage. The intestinal flora profile may be protective against CRC but is altered when processed and ultra-processed foods are included in the diet. Fiber, phytochemicals, and spices present in plant foods are consistently reported to have anticarcinogenic effects.

Integrative analysis of causal associations between neurodegenerative diseases and colorectal cancer

BackgroundObservational studies have shown that the correlation between neurodegenerative diseases and colorectal cancer (CRC) remains controversial. Therefore, this study aimed to verify the causal association between these two diseases. MethodsMendelian randomization (MR) analysis was used to assess the causal relationships between five major neurodegenerative diseases and CRC. Multivariable MR (MVMR) analysis was conducted to assess the direct causal effect of neurodegenerative diseases on CRC. Colocalization and pathway enrichment analyses were conducted to further elucidate our results. Sensitivity analysis was conducted to assess the robustness of the results. ResultsGenetically predicted Alzheimer's disease (AD) nominally increased CRC risk (OR = 1.0620, 95%CI = 1.0127–1.1136, P = 0.013). There was no causal effect of genetically predicted CRC on neurodegenerative diseases. Furthermore, we demonstrated that genetically predicted AD marginally increased colon cancer risk (OR = 1.1621, 95%CI = 1.0267–1.3153, P = 0.017). Genetically predicted Lewy body dementia (LBD) had a significant causal effect on the increasing risk of colon cancer (IVW OR = 1.1779, 95%CI = 1.0694–1.2975, P = 0.001). MVMR indicated that effect of AD on colon cancer was driven by LBD, type 2 diabetes, body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, total cholesterol (TC), processed meat consumption, smoking, alcohol consumption, and educational attainment, whereas the effect of LBD on colon cancer was only influenced by TC. Colocalization and pathway enrichment analysis suggested that LBD and colon cancer possibly shared causal variants (nearby gene APOE), and ERBB4 signaling and lipid metabolism may mediate the causal association between LBD and colon cancer. Sensitivity analysis confirmed the reliability of our findings. ConclusionsOur study demonstrated that genetic vulnerabilities to AD nominally increased the overall risk of CRC and colon cancer. Genetically predicted LBD indicated an elevated risk of colon cancer, potentially linked to ERBB4 signaling and lipid metabolism.

Income dynamics and risk of colorectal cancer in individuals with type 2 diabetes: a nationwide population-based cohort study.

Individuals with type 2 diabetes (T2D) have increased colorectal cancer (CRC) risk, but it is unknown whether income dynamics are associated with CRC risk in these individuals. We examined whether persistent low- or high-income and income changes are associated with CRC risk in non-elderly adults with T2D. Using nationally representative data from the Korean Health Insurance Service database, 1,909,492 adults aged 30 to 64 years with T2D and no history of cancer were included between 2009 and 2012 (median follow-up of 7.8 years). We determined income levels based on health insurance premiums and assessed annual income quartiles for the baseline year and the four preceding years. Hazard ratios(HRs) and 95% confidence intervals(CIs) were estimated after adjusting for sociodemographic factors, CRC risk factors, and diabetes duration and treatment. Persistent low income (i.e., lowest income quartile) was associated with increased CRC risk (HRn=5years vs. n=0years 1.11, 95% CI 1.04-1.18; P for trend=0.004). Income declines (i.e., a decrease≥25% in income quantile) were also associated with increased CRC risk (HR≥2 vs. 0 declines 1.10, 95% CI 1.05-1.16; p for trend=0.001). In contrast, persistent high income (i.e., highest income quartile) was associated with decreased CRC risk (HRn=5years vs. n=0years 0.81, 95% CI 0.73-0.89; p for trend<0.0001), which was more pronounced for rectal cancer (HR 0.64, 95% CI 0.53-0.78) and distal colon cancer (HR 0.70, 95% CI 0.57-0.86). Our findings underscore the need for increased public policy awareness of the association between income dynamics and CRC risk in adults with T2D.

Levels of 5α-reductase gene in intestinal lavage fluid decrease with progression of colorectal cancer.

Introduction. Colorectal cancer (CRC) is a leading cause of cancer deaths, closely linked to the intestinal microbiota and bile acid metabolism. Secondary bile acids, like deoxycholic and lithocholic acid, are associated with increased CRC risk due to their disruption of vital cellular functions. In contrast, isoallolithocholic acid (isoalloLCA) shows potential health benefits, highlighting the complex role of bile acids in CRC. A specific primer set was previously developed to amplify homologs of the 5α-reductase gene (5ar), which are involved in the biosynthesis of isoalloLCA, thereby enabling the estimation of abundance of 5ar (5ar levels) in the intestine.Hypothesis/Gap Statement. We hypothesized that 5ar levels in the intestine are associated with CRC.Aim. This study aimed to investigate intestinal 5ar levels and compare them across different stages of the adenoma-carcinoma sequence, providing insights into novel strategies for monitoring CRC risk.Methodology. DNA was extracted from intestinal lavage fluids (ILF) collected during 144 colonoscopies. Next-generation sequencing (NGS) was employed to examine the sequence of 5ar homologues, using a specific primer set on DNA from seven selected ILFs - four from carcinoma patients and three from individuals with non-neoplastic mucosa. Additionally, we used quantitative PCR (qPCR) to measure 5ar levels in all 144 DNA samples.Results. We conducted 144 colonoscopies and categorized patients according to the adenoma-cancer sequence: 52 with non-neoplastic mucosa, 69 with adenomas and 23 with carcinoma. Analysis of 292,042 NGS-derived 5ar sequences revealed the seven most prevalent amplicon sequence variants, each 254 base pairs in length. These closely matched or were identical to 5ar sequences in Bacteroides uniformis, Phocaeicola vulgatus and Phocaeicola dorei. Furthermore, qPCR analysis demonstrated significantly lower 5ar levels in the carcinoma group compared to those in the non-neoplastic mucosa group (P = 0.0004). A similar, though not statistically significant, trend was observed in the adenoma group (P = 0.0763), suggesting that 5ar levels decrease as CRC progresses.Conclusion. These findings indicate that PCR-based monitoring of 5ar levels in intestinal samples over time could provide a non-invasive, rapid and cost-effective method for assessing an increased risk of CRC.

The association between ambient air pollution and colorectal cancer: a Mendelian randomization study

ABSTRACT Mounting epidemiology studies have reported the potential associations between ambient air pollution exposure and colorectal cancer (CRC). However, the genetic association between ambient air pollution and CRC remains unclear. Using the Genome-wide association study (GWAS) data from UK biobank, we explored the genetic association of CRC (5,657 cases and 372,016 controls) with four ambient air pollutants (PM2.5, PM10, NO2, NOx; n = 423,796 to 456,380) under the framework of Mendelian randomization (MR). Our results revealed a significant association between long-term NO2 exposure (per 10 µg/m3) and increased CRC risk, with an odds ratio (OR) of 1.02 (95% confidence interval [CI]: 1.00–1.03), while no statistical association was found between CRC risk and the other air pollutants. Sensitivity analysis confirmed the robustness of the results. It is imperative to consider the impact of air pollution, particularly NO2, in mitigating the risk of CRC.

Genetic Evidence for a Causal Relationship Between Innate Leukocytes and the Risk of Digestive System Cancers in East Asians and Europeans.

Peripheral traditional immune cell disorder plays an important role in cancer onset and development. The causal relationships between leukocytes prior to cancer and the risk of digestive system cancer remain unknown. This study assesses the causal correlations between leukocytes and digestive system cancer risk in East Asians and Europeans. Summary-level data on leukocyte-related genetic variation were extracted from Biobank Japan (107,964 participants) and a recent large-scale meta-analysis (563,946 participants). Summary-level data for the cancers were obtained from Biobank Japan (212,978 individuals) and the FinnGen consortium (178,802 participants). Univariable and multivariable Mendelian randomization (MR) analyses were performed on East Asians and Europeans separately. Univariable MR analysis demonstrated the significant association between circulating eosinophil counts and risk of colorectal cancer (CRC) in East Asians (odds ratio (OR) = 0.80, 95% confidence interval (CI): 0.69 - 0.92, P = 0.002) and a suggestive relationship in the European population (OR = 0.86, 95% CI: 0.77 - 0.97, P = 0.013). An inverse suggestive association was observed between levels of basophils and the risk of gastric cancer (GC) in East Asians (OR = 0.83, 95% CI: 0.72 - 0.97, P = 0.019). The multivariable MR analysis showed the independent causal effect of eosinophil count on CRC risk in East Asians (OR = 0.72, 95% CI: 0.57 - 0.92, P = 0.009) and Europeans (OR = 0.80, 95% CI: 0.70 - 0.92, P = 0.002). Circulating basophils served as the negative causal factor in GC risk in East Asians (OR = 0.80, 95% CI: 0.67 - 0.94, P = 0.007). Our MR analyses revealed a genetic causal relationship between reduced blood eosinophils and an increased CRC risk in both Europeans and East Asians. Furthermore, our results suggested a causal association between decreased basophils and an elevated GC risk specifically in East Asians.

Mexican physicians' knowledge and attitudes towards hereditary colorectal cancer risk management.

e22552 Background: Genetic cancer risk assessment (GCRA) has become an integral component of the management of patients with colorectal cancer (CRC). Understanding clinical criteria and interpreting screening tests to identify patients who should be prioritized for genetic testing is especially critical in resource-constrained settings such as Mexico, where access to genetic testing is limited. Methods: We designed a self-applicable survey consisting of 18 items, divided into three sections: 7 on knowledge, 5 on clinical approaches, and 6 on access to genetic testing. The aim was to assess the practice patterns of Mexican physicians in contact with patients at risk for hereditary CRC. Initially, the survey was piloted among oncology fellows to refine and improve its relevance and applicability. Following adjustments, it was disseminated using a QR code at the annual meeting of the Mexican Society of Oncology (SMeO) in September 2023. Descriptive statistics were performed using frequency and proportions for categorical variables and median and range for quantitative variables. Results: A total of 78 physicians completed the survey, with a median age of 37 years (range, 27-70). Among them, 47.2% were female, 82% were medical oncologists, with a median practice duration of 6 years (range, 1- 40). 52.6% practice in cancer community centers, 83.4% were employed in public primary care settings, and 60% were affiliated to academic centers. Referral criteria for GCRA was identified correctly in 66.7% who recognized age at CRC diagnosis &lt; 50 years, 57.7% synchronous or metachronous CRC, 50% deficient mismatch repair CRC, and 37.2% PREMM5 score of ≥2.5%. Lynch syndrome, Familial Adenomatous Polyposis (FAP), and Cowden syndrome were identified as syndromes with an increased CRC risk by 76.9%, 71.8% and 56.7% of respondents, respectively. Decision-making based on likely pathogenic and pathogenic variants was indicated by 26.9% and 69.2%, while 12.8% reported making decisions based on variants of uncertain significance (VUS). Regarding clinical approach, 74.4% inquired about a family history of cancer at the initial consultation, and 66.7% referred patients for genetic counseling. The primary obstacles to accessing GCRA were the cost of genetic testing (43.6%) and the absence of medical genetics services at their centers (39.7%). Only 23% reported the availability of cascade testing within their practice. Conclusions: The identification of patients at risk of hereditary CRC was suboptimal among Mexican physicians. A high proportion of respondents were not fully qualified to interpret correctly genetic testing results. These indicate a need for awareness and educational programs to improve providers’ knowledge on predisposition cancer syndromes.

The association of the killer cell immunoglobulin-like receptor (KIR) genotype distribution and HLA-C ligands in colorectal cancer in the eastern region of Saudi Arabia

Colorectal cancer (CRC) is the most common cause of cancer-related mortality globally. It ranks as the most common cancer among men and the third most prevalent among women in Saudi Arabia, especially in the eastern region. The immune system's response to cancer is significantly influenced by natural killer cells through their killer-cell immunoglobulin-like receptors (KIRs) interaction with human leukocyte antigen (HLA) molecules. Our research aimed to target a homogeneous ethnic group in the eastern region of Saudi Arabia, analyzing the distribution of 16 KIR genes and HLA-C1/C2 allotypes in 50 CRC patients and 63 healthy controls using the sequence-specific PCR amplification method. Findings revealed significantly lower frequencies of the 2DL2 and 3DL1 genes in CRC patients compared to controls (OR = 2.21; P = 0.04) and (OR = 7.46; P = 0.00009), respectively. Additionally, a higher prevalence of HLA-C2 was noted in CRC patients (84 %) versus controls (66.7 %) (OR = 2.26; P = 0.04). Conversely, the HLA-C1C2 combination showed a protective effect against CRC (OR = 0.38; P = 0.04). Our combinatorial analysis further identified specific gene combinations correlating with CRC risk or protection. Notably, the absence of KIR2DL2 combined with the presence of KIR2DS2 emerged as a significant risk factor, while various combinations involving KIR2DL2 and/or KIR2DS1 with HLA-C ligands were associated with either increased susceptibility or protection. The study underscores the protective role of KIR2DL2 against CRC in Saudi Arabia's eastern region and suggests that the absence of KIR2DL2, especially when KIR2DS2 is present, might increase CRC risk. This research contributes to understanding genetic influences on CRC susceptibility, emphasizing the potential of KIR and HLA interactions as biomarkers for CRC risk assessment.