Risk Of Colorectal Cancer Research Articles

Exploring the Chemopreventive Effect of Medication on Gene Expression Linked to Colorectal Cancer: An Observational and Mendelian Randomization Analysis in Healthy Colon Mucosa.

Gene expression appears altered in apparently normal tissue surrounding tumor tissue. The observed biological alterations in the tumor microenvironment play a crucial role in cancer development and are named the cancer field effect (FE). A robust set of overexpressed FE genes in tissue surrounding colorectal cancer (CRC) tumor were identified in previous studies. Our study aimed to investigate the influence of common medication intake and modifiable risk factors on FE gene expression using a colonic mucosa sample dataset of healthy individuals (BarcUVa-Seq). We applied expression enrichment analysis of the FE genes for each studied medication and factor. Both observational and instrumental (Mendelian randomization) analysis were conducted, and the results were validated using independent datasets. The findings from the observational and instrumental analyses consistently showed that medication intake, especially metformin, considerably downregulated the FE genes. Chemopreventive effects were also noted for antihypertensive drugs targeting the renin-angiotensin system. Conversely, benzodiazepines usage might upregulate FE genes, thus fostering a tumor-promoting microenvironment. In contrast, the findings from the observational and instrumental analyses on modifiable risk factors showed some discrepancies. The instrumental results indicated that obesity and smoking might promote a tumor-favorable microenvironment. These findings offer insights into the biological mechanisms through which risk factors might influence CRC development and highlight the potential chemopreventive roles of metformin and antihypertensive drugs in CRC risk.

Sodium Butyrate as Gut Microbiota Modulators: Mechanisms of Action and Potential Clinical Applications - Literature Review and New Perspectives

IntroductionSodium butyrate is an organic chemical compound belonging to sodium salts, which has the potential to be used in anticancer therapy. It reduces inflammation of the intestinal mucosa and promotes the development of beneficial intestinal flora, thanks to which it helps maintain homeostasis. Therefore, butyrate reduces the risk of developing colon cancer or reverses pathological changes occurring under the influence of this cancer. Scientific studies have also shown a beneficial effect of butyrate on the side effects of anticancer treatment - chemotherapy and radiotherapy. A proper diet also has a beneficial effect on the production of endogenous butyrate and reduces the risk of developing colon cancer. It is recommended to use a Mediterranean diet, rich in dietary fiber, highly unsaturated fatty acids and fresh vegetables and fruits. It is recommended to avoid highly processed products, rich in simple sugars and saturated fatty acids, and to limit the consumption of red meat. Materials and methods This article is based on the literature found in the PubMed and other scientific databases from the period of 1978-2023 with the use of key words such as “butyrate” “sodium butyrate” “colon cancer” “anticancer treatment” “intestinal microbiota” “Mediterranean diet” Conclusion Sodium butyrate is a potential substance that, through its properties, may support the treatment of colorectal cancer. Additionally, the use of an appropriate diet has a positive effect on the intestinal microflora, allowing the action of sodium butyrate and reducing the risk of colorectal cancer.

MiR-559 rs58450758 polymorphism is associated with colorectal cancer risk and prognosis in Chinese Han population.

Aim: This research examined the correlation between miR-559 rs58450758 and the clinical pathological characteristics and prognosis of CRC.Materials & methods: RT-qPCR was utilized to assess the miR-559 expression levels. Chi-square test was used to investigate the relationship between miR-559 and clinical features. The association between rs58450758 different genotypes and CRC risk, as well as clinical pathological parameters, was explored, utilizing logistic regression analysis and chi-square tests. The Cox regression model and Kaplan-Meier analysis evaluated overall survival in individuals with CRC.Results: The miR-559 was down-regulated in CRC patients' serum. The expressions of miR-559 were significantly associated with tumor size, differentiation, TNM stage and lymph node metastasis. The rs58450758 TT genotype and T allele carriers were more prevalent among CRC patients. The rs58450758 polymorphism was notably linked to tumor size, differentiation, TNM stage and lymph node metastasis in CRC patients. Furthermore, CC genotype carriers exhibited a longer survival period than CT/TT genotypes within the CRC population.Conclusion: The miR-559 rs58450758 polymorphism exhibits promise as a potential biomarker for prognosticating the outcomes of CRC.

Development and validation of machine learning models for young-onset colorectal cancer risk stratification

Incidence of young-onset colorectal cancer (YOCRC, younger than 50) has significantly increased worldwide. The performance of fecal immunochemical test in detecting YOCRC is unsatisfactory. Using routine clinical data, we aimed to develop machine learning (ML) models to identify individuals with high-risk YOCRC who require further colonoscopy. We retrospectively extracted data of 10,874 young individuals. Multiple supervised ML techniques were devised to distinguish individuals with and without CRC, classifiers were trained, internally validated and temporally validated. In internal validation cohort, Random Forest (RF) ML model demonstrated good performance with AUC of 0.859 and highest recall of 0.840. In temporal validation cohort, the RF ML model also exhibited good classification performance, achieving AUC of 0.888 and highest recall of 0.872. RF algorithm-based approach is effective and feasible in YOCRC risk stratification. This could be valuable in assessing the risk of YOCRC so that clinical management, including further colonoscopy, can be subsequently made. (Registration: This study was registered with ClinicalTrials.gov (NCT06342622) on March 15, 2024.).

Effects of simultaneous intake of dietary fermented foods and processed meat products on the risk of colorectal cancer

AbstractThis study investigated the effects of fermented food consumption on the risk of colorectal cancer (CRC) related to processed meat intake using a mouse model. Processed meat products and fermented foods were supplemented to analyze heterocyclic amines (HCA) and carcinoembryonic antigen (CEA) levels and the gut microbiota in mice. The study determined age to be a non‐influential factor. While HCAs were detected in all the processed meat samples, no CRC development was observed, even when they consumed excessive amounts of these processed meats, either alone or in combination with fermented foods. Bacteroides and Alistipes were the most predominant gut microbiota. Kimchi, soybean paste, and red pepper paste showed a decreasing trend in the ratio of these bacteria associated with gut inflammation, but the results were inconclusive because this trend was inconsistent. Therefore, this study found that fermented foods did not significantly affect CRC risk indicators associated with dietary processed meat intake, regardless of age.

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.

The association between empirical dietary inflammatory pattern and risk of cancer and cancer-specific mortality: a systematic review and meta-analysis of prospective cohort studies.

Current evidence indicates a correlation between the inflammatory potential of diet and the risk of cancer and cancer-specific mortality. This study aimed to assess the association between empirical dietary inflammatory pattern (EDIP), which has recently been designed based on the inflammatory potential of the diet, and the risk of cancer and cancer-specific mortality. A systematic literature search was conducted across the PubMed/Medline, Scopus, and Web of Science databases from January 2016 to March 2024. A random effects model was used to calculate the pooled effect size (ES) and 95% confidence intervals (95% CI). Heterogeneity between studies was assessed using the Cochran Q test and the I 2 statistic. From the initial 229 records, 24 prospective cohort studies with 2,683,350 participants and 37,091 cancer incidence cases, as well as 20,819 cancer-specific mortality, were included in our study. Pooled results indicated a significant association between higher adherence to the EDIP and an increased risk of total cancer (ES: 1.10; 95% CI: 1.05-1.15; I 2 = 41.1), colorectal cancer (ES: 1.19; 95% CI: 1.11-1.27; I 2 = 41.1), and liver cancer (ES: 1.48; 95% CI: 1.14-1.94; I 2 = 36.9). However, no significant association between increased adherence to the EDIP and an increased risk of ovarian or endometrial cancer was found. Furthermore, greater adherence to the EDIP was significantly associated with an increased risk of cancer-specific mortality (ES: 1.18; 95% CI: 1.05-1.33; I 2 = 45.4). Our results showed that a diet with higher inflammatory properties is associated with an increased risk of cancer and cancer-specific mortality. PROSPERO registration no. CRD42024496912.

Lifestyle, dietary pattern and colorectal cancer: a case-control study

BackgroundIn Iran, not only the incidence of colorectal cancer (CRC) is increasing but also the age of patients at diagnosis is alarmingly dropping. We need urgent actions to better understand the epidemiology of CRC and the contributing factors for such pattern in Iranian population. The aim of our study was to determine the potential contribution of lifestyle, including dietary pattern, to CRC in a large Iranian province.MethodsA hospital based case-control study was performed on 572 participants (275 cases and 297 controls). Patients in the case group were newly diagnosed with CRC in a referral hospital and patients in the control group were selected from those patients with non-malignancy diseases who were admitted to the same hospital. Control group was frequency matched to the case group for gender and age.ResultsBased on the results of multivariable logistic regression analysis, direct associations were observed between usual pattern of defecation (OR> 3rd /every day =4.74, 95% CI: 1.78–12.59), chicken consumption (ORsometimes or always/occasionally = 6.33, 95% CI:3.23–12.43), family history of CRC (ORyes/no =5.79, 95% CI: 2.72–12.31), and alcohol consumption (ORyes/no =6.03, 95% CI: 2.14–16.98) with the odds of CRC among the study population. On the other hand, taking multivitamins (ORyes/no=0.09, 95% CI:0.04–0.20), consumption of coffee (ORalways/occasionally =0.29, 95% CI: 0.12–0.69), taking vitamins D supplement (ORyes/no =0.38,95% CI:0.22–0.66), and consumption of garlic (ORsometimes/occasionally =0.53,95% CI: 0.30–0.95) significantly reduced the odds of CRC.ConclusionsWe revealed potentially significant effects of several lifestyle related factors with CRC risk in Iranian population. More studies are required to understand the mechanism of action of the associated factors in developing CRC.

The Relationship Between miR-196a2 Polymorphism and Colorectal Cancer Risk

ABSTRACT Objective MicroRNAs are small endogenous, non-coding, single-stranded posttranscriptional RNA molecules. The discovery of microRNAs has made new contributions to cancer diagnosis and treatment. These microRNAs reported as a responsible for colorectal cancer development with several epigenetic changes. In this study, it was aimed to evaluate the relationship between the polymorphism of miR-196a-2 polymorphism rs11614913 and colorectal cancer in Turkish population. Methods Two hundred colorectal cancer patient (124 colon cancer and 76 rectal cancer) and 240 health control individuals were included in our study, which was planned as a hospital based retrospective cohort study. MiR-196a2 polymorphism in peripheral blood samples has been determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) method. Significance of the results has been evaluated by using SPSS (20.0 SPSS Inc., Chicago, IL, USA.) statistical program. Results miR-196a2 C / C + C / T genotypes was found to be associated with the risk of colorectal cancer development (p: 0.001; OR: 2.04, 95% CI: 1.293-3.236). The subgroup analysis, showed that the C / C + C / T genotype increased the risk of colon cancer development 2.11 times (p: 0.016; 95% CI: 1.136-3.918) and rectal cancer 2.86 times (p: 0.011; 95% CI:1.242-6.592). The relationship between any clinicopathological features of colorectal cancer and the frequency of the C / C + C / T genotype of miR196a2 was not statistically significant (p&gt; 0.05). Conclusion This study supports that miR-196a2's C / C + C / T genotypes is related with increased colorectal cancer development risk.

Association of eczema with risk of pan-cancers: a two-sample Mendelian randomization study

Abstract Background Both eczema and tumor are associated with immune disorders. Although several investigations have observed the relationship between eczema and certain cancers, evidence for causality is lacking. Methods We conducted a two-sample Mendelian randomization (MR) study to examine and explore the genetic association between eczema and pan-cancers. Upon satisfying the three core assumptions of MR, we analyzed the causality between eczema and 15 site-specific cancers utilizing an inverse variance weighted method. We verified the results through a series of sensitivity and reverse direction analyses. The exposure and outcome datasets were substituted from the FinnGen and genome-wide association studies catalog databases. A meta-analysis on primary and validation analyses was performed to combine the estimates of MR study. Results Based on the MR analysis results, eczema was associated with an increased risk of lung cancer (odds ratio [OR] = 1.0427, 95% confidence interval [CI] = 1.0082–1.0783, P = 0.0148) and brain cancer (OR = 1.0285, 95% CI = 1.0120–1.0452, P = 0.0007) and decreased risk of colorectal cancer (OR = 0.9324, 95% CI = 0.8774–0.9909, P = 0.0242) and malignant neoplasm of the kidney (OR = 0.9323, 95% CI = 0.8834–0.9839, P = 0.0108). The sensitivity analysis indicated that the results were stable and reliable, and the reverse MR analyses demonstrated no causation between the cancers of interest and eczema. Conclusions Our results identified eczema as a genetic risk factor for lung and brain cancer and a protective factor for colorectal cancer and malignant neoplasm of the kidney. No connection was observed between eczema and other cancers. Further evidence from epidemiological and mechanistic studies is needed to elucidate these findings in detail.

Screening participants with inflammatory bowel disease or high colorectal cancer risk in Denmark: a cohort study.

Individuals with inflammatory bowel disease (IBC) and high-risk individuals are advised to discuss participation with their doctor and not to participate in colorectal cancer (CRC) screening. Yet a substantial proportion still participate in the Danish faecal immunochemical test (FIT) screening and have a higher positive FIT rate than the average-risk population. We estimated the risk of false-positive screening among individuals with inflammatory bowel disease and high-risk individuals to improve recommendations regarding screening participation. We included 71,871 FIT-positive participants (2014-2017) who had a subsequent colonoscopy within 3 months. Screening outcome within 180 days was established by using registers. We determined that 26,591 of the included participants had a false-positive screening. Participants with IBC or high CRC risk had a significantly higher risk of getting a false-positive screening than the average risk population, resulting in too many screening-related colonoscopies being performed among these individuals, indicating a need to update the screening protocols.

Solitary Loss of PMS2 in a patient with Colon carcinoma

Abstract Introduction/Objective In the United States, there are about 150,000 new cases of Colorectal cancer (CRC) and about 50,000 CRC related deaths each year. Hereditary nonpolyposis colorectal cancer (Lynch Syndrome) accounts for 2% - 4% of CRC. It is characterized by germline mutations in mismatch repair (MMR) genes - MLH1, MSH2, MSH6 and PMS2. Patients with Lynch syndrome have up to an 80% lifetime risk (LTR) of CRC and up to 60% LTR of endometrial cancer. Lynch syndrome patients also have an associated LTR of ovarian cancer (38%), upper urologic tract cancer (18%), gastric cancer (13%), small bowel cancer (6%), hepatobiliary tract cancer (4%), and brain tumors (3% - usually glioblastoma). Methods/Case Report A 76-year-old man with history of moderately differentiated colorectal adenosarcoma involving the transverse colon and a recently diagnosed grade group 5 (Gleason 4 + 5) prostate adenocarcinoma, currently being managed at an outside hospital. The case was sent to UAB for DNA MMR/microsatellite instability (MSI) status evaluation testing. Immunostaining showed loss of PMS2 and intact expression of MLH1, MSH2 and MSH6. These results were confirmed by the IdyIIa MSI assay which detected microsatellite instability in 5 of 7 markers and negative for BRAF V600E variant confirming microsatellite instable tumor. Results (if a Case Study enter NA) NA Conclusion Solitary loss of PMS2 in colonic adenocarcinoma is uncommon and may be caused by an underlying germline mutation of MLH-1 or PMS2, thus could represent Lynch Syndrome. Our patient’s age doesn’t favor Lynch syndrome. Next step would be to perform MLH-1 promoter methylation to confirm sporadic nature of carcinoma. Somatic methylation of the MLH1 promoter occurs in approximately 80% of CRC with defective MMR. Prostate cancer is not currently considered a part of Lynch syndrome.

Immunomodulatory effect of Dicrocoelium dendriticum ova on DSS-induced experimental colitis in C57BL/6 mouse

Inflammatory bowel disease (IBD) significantly diminishes an individual’s quality of life and increases the risk of colorectal cancer. Recent clinical and experimental findings suggest that infection with parasitic helminths may suppress the development of certain inflammatory conditions. The objective of this study was to evaluate the immunoregulatory effects of Dicrocoelium eggs on experimentally induced colitis in C57BL/6 mice using dextran sulfate sodium (DSS). C57BL/6 mice received 3.5% DSS orally for 7 days to induce colitis, during which they were treated intraperitoneally with Dicrocoelium eggs. The severity of colitis was assessed through parameters such as body weight, stool consistency or bleeding, disease activity index (DAI), colon lengths, macroscopic scores, histopathological findings, colon gene expression levels, and serum cytokine levels. Our results indicated that Dicrocoelium eggs administration significantly reduced the severity of colitis and disease activity. Histopathological scores improved, correlating with downregulation of IFN-γ and upregulation of IL-4 expression. This findings suggest the therapeutic potential of Dicrocoelium eggs in treating colitis. Immunotherapy involving Dicrocoelium eggs primarily induces a Th2 response and modulates IFN-γ, contributing to reduced inflammation in colitis. Thus, this approach could be a promising therapeutic strategy for alleviating inflammation in IBD.

Prediction of metachronous advanced colorectal neoplasia by KRAS mutation in polyps.

The potential of molecular markers in the removed polys as reliable predictors of metachronous lesions is still uncertain. Our aim was to evaluate the role of somatic mutations in KRAS in polyps of patients with high-risk adenomas to predict the risk of advanced polyps or colorectal cancer (CRC) within 3 years. A total of 518 patients were prospectively enrolled. The included patients had adenomas ≥10mm, high-grade dysplasia, villous component or ≥3 more adenomas at baseline and were scheduled to undergo surveillance colonoscopy at 3years±6months. Somatic KRAS mutation was performed on 1189 polyps collected from these patients. At surveillance, advanced lesions were defined as adenomas with a size of ≥10mm. High-grade dysplasia or villous component, serrated polyps ≥10mm or with dysplasia or CRC. At baseline, 81 patients (15.6%) had KRAS mutations in at least one polyp. Patients with KRAS mutated polyps had more frequent villous histological lesions and size ≥20mm. In the multivariate analysis, adjusted for age and sex, only age (odds ratios [OR], 1.06; 95% confidence interval [CI], 1.02-1.09; p<0.001), ≥5 adenomas (OR, 3.92; 95% CI, 1.96-7.82), and KRAS mutation (OR, 2.54; 95% CI, 1.48-4.34; p<0.01) were independently associated with the development of advanced lesions at surveillance. Our results show that, in patients with high-risk adenomas, the presence of somatic mutations in KRAS is an independent risk factor for the development of advanced metachronous polyps.

Sex hormones and risk of lung and colorectal cancers in women: a Mendelian randomization study

The roles of sex hormones such as estradiol, testosterone, and sex hormone-binding globulin (SHBG) in the etiology of lung and colorectal cancers in women, among the most common cancers after breast cancer, are unclear. This Mendelian randomization (MR) study evaluated such potential causal associations in women of European ancestry. We used summary statistics data from genome-wide association studies on sex hormones and from the Trøndelag Health Study (HUNT) and large consortia on cancers. There was suggestive evidence of 1-standard deviation increase in total testosterone levels being associated with a lower risk of lung non-adenocarcinoma (hazard ratio 0.60, 95% confidence interval 0.37–0.98) in the HUNT Study. However, this was not confirmed by using data from a larger consortium. In general, we did not find convincing evidence to support a causal role of sex hormones on risk of lung and colorectal cancers in women of European ancestry.

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.

Family History of Colorectal Cancer and the Risk of Colorectal Neoplasia: A Systematic Review and Meta-Analysis.

Although there is enough pooled evidence supporting the positive association between family history of colorectal cancer (CRC) in first-degree relatives (FDRs) and the risk of CRC, synthesized data on its association with the risk of other colorectal neoplasia are lacking. Therefore, we aimed to systematically assess this issue. We searched PubMed, Web of Science, and Embase from database inception through May 9, 2024, to identify observational studies investigating the association between family history of CRC in FDRs and the risk of colorectal neoplasia (excepting CRC). Adenoma, nonadvanced adenoma (NAA), advanced adenoma (AA), and advanced neoplasia (AN) were further chosen as main outcomes because of data availability. Random-effects model was used for data synthesis. Subgroup meta-analyses were performed to evaluate the robustness of results. Of 5,172 initial records screened, 75 studies (with 931,515 participants) were identified for analysis. Family history of CRC in FDRs was associated with increased risk of adenoma (pooled odds ratio [OR] 1.67, 95% confidence interval [CI] 1.46-1.91), NAA (pooled OR 1.35, 95% CI 1.21-1.51), AA (pooled OR 1.66, 95% CI 1.46-1.88), and AN (pooled OR 1.58, 95% CI 1.44-1.73). The positive associations persisted in all examined subgroups. The risk of adenoma (pooled OR 4.18, 95% CI 1.76-9.91), AA (pooled OR 2.42, 95% CI 1.72-3.40), and AN (pooled OR 2.00, 95% CI 1.68-2.38) was more evident among individuals with 2 or more affected FDRs. Family history of CRC is associated with increased risk of adenoma, NAA, AA, and AN totally, and in all available subgroups. The findings further strengthen the necessity and importance of an intensified screening strategy for individuals with a positive family history of CRC, which is very useful for related health resource allocation and policymaking.

Serum bilirubin levels and risk of colorectal cancer in Korean adults: results from the Korean Genome and Epidemiology Study-Health Examinee (KoGES-HEXA) Cohort Study.

Current evidence on associations between circulating bilirubin and colorectal cancer (CRC) risk is inconsistent. In this prospective study, we investigated associations of pre-diagnostic circulating levels of total and indirect bilirubin with CRC risk in 78,467 Korean adults aged 40-78 years at recruitment, considering potential non-linearity and sex differences. Hazard ratios (HR) and 95% confidence intervals (CI) for associations with CRC risk were estimated with Cox proportional hazard regression. During a median 7.9-year follow-up, 539 incident CRC cases were recorded. In multivariable-adjusted models, higher levels of total bilirubin were associated with a 26% (CI: 42% to 7%) lower risk of CRC among men and women combined, comparing the highest with the lowest tertile (P-linear trend = 0.003). A U-shaped association was observed in men, with the lowest risk at approximately 0.8 mg/dL (=13.7 μmol/L) of total bilirubin (P for non-linearity = 0.01). Although the association was largely null in women, there was no evidence for effect modification by sex (P-interaction = 0.73). Associations between indirect bilirubin and CRC risk were similar. Higher circulating levels of total and indirect bilirubin were inversely associated with the risk of CRC among Korean adults. The associations were strongly inverse and U-shaped among men.

Overweight and obesity significantly increase colorectal cancer risk: a meta-analysis of 66 studies revealing a 25-57% elevation in risk.

The incidence of colorectal cancer (CRC) has been steadily rising, and obesity has been identified as a significant risk factor. Numerous studies suggest a strong correlation between excess body weight and increased risk of CRC, but comprehensive quantification through pooled analysis remains limited. This study aims to systematically review and meta-analyze the existing literature to evaluate the association between obesity and CRC risk, considering variations across sex and study designs. A systematic literature search was conducted in PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science to identify randomized controlled trials and human clinical trials from 1992 to 2024. Statistical analysis was performed using the https://metaanalysisonline.com web application using a random effects model to estimate the pooled hazard rates (HR). Forest plots, funnel plots, and Z-score plots were utilized to visualize results. We identified 52 clinical trials and 14 case-control studies, encompassing a total of 83,251,050 and 236,877 subjects, respectively. The pooled analysis indicated that obesity significantly increased the prevalence of CRC (HR = 1.36, 95% CI = 1.24-1.48, p < 0.01). This effect was consistent across sexes, with HRs of 1.57 (95% CI = 1.38-1.78, p = 0.01) for males and 1.25 (95% CI = 1.14-1.38, p < 0.01) for females. Case-control studies specifically showed an effect, but with marginal significance only (HR = 1.27, 95% CI = 0.98-1.65, p = 0.07). The Z-score plot indicated the need for additional analysis in the case-control group. A significant heterogeneity was observed across studies in all four settings. This meta-analysis provides robust evidence that obesity is a significant risk factor for colorectal cancer, with an overall hazard rate indicating a 36% increased risk. The effect is pronounced across both sexes, with males showing a slightly higher risk compared to females. Although case-control studies showed a weaker association, the overall trend supports the link between obesity and CRC. These results underscore the importance of public health interventions aimed at reducing obesity to potentially lower the risk of colorectal cancer.

Evaluation of the Danish Colorectal Cancer Screening Program Among People With Cystic Fibrosis.

We aimed to evaluate the Danish CRC screening program, estimate colonic neoplasia's prevalence, and assess the utilized BP regimens. People with cystic fibrosis (pwCF) have an increased risk of precancerous polyps and colorectal cancer (CRC), with occurrence at an earlier age compared with the general population. Consequently, colonoscopy screening is recommended. PwCF requires specific bowel preparation (BP) regimens to ensure an adequate colonoscopy. We conducted a national retrospective cohort study, which included all pwCF eligible for colonoscopy according to international recommendations in 26 months. Among 119 eligible pwCF, 58 completed colonoscopies during the screening period. The screening was omitted in 25% of pwCF. Among the pwCF undergoing colonoscopy screening, precancerous polyps were found in 24% and none with CRC. One patient developed CRC before being offered screening. Risk factors for neoplasia were old age and male sex. The quality of BP was high, even though most pwCF received standard BP. The best quality was found in nonorgan transplanted, pwCF who received modulator treatment and those with no laxatives use. We detected a high adherence to CRC screening, but also a substantial proportion of pwCF who were not informed about screening recommendations, calling for greater awareness among clinicians. Although lower than previously described, our study revealed high numbers of precancerous polyps and CRC compared with the general population, underlining the need for screening. BP quality remained high, despite frequent use of standard regimens, implicating the need for more individualized regimens before undergoing colonoscopy.