UNASSIGNED: Colonoscopy is imperfect for colorectal cancer (CRC) prevention. Postcolonoscopy CRC (PCCRC) is defined as CRC detected after a screening or surveillance colonoscopy. PCCRCs can be divided into noninterval CRC and interval CRC. We performed a case-control study to identify risk factors for PCCRCs and to compare risks between noninterval and interval PCCRCs.
UNASSIGNED: We designed a retrospective case-control study. Using a Vermont tumor registry data set, we identified all PCCRCs diagnosed at our medical center from January 2012 to September 2017. Cases were matched 1:3 with controls of the same age, sex, and index colonoscopy date.
UNASSIGNED: Fifty-four PCCRCs were matched with 162 controls and divided into noninterval (N = 27) and interval (N = 27) subsets. Overall PCCRC risk and noninterval PCCRC risk were significantly associated with history of polyps (odds ratio [OR] PCCRC = 2.71, OR noninterval = 4.41), sessile serrated polyps (OR PCCRC = 3.94, OR noninterval = 5.79), and high-risk adenoma (HRA) (OR PCCRC = 6.58, OR noninterval = 16.46) and with the index colonoscopy having a large polyp (OR PCCRC = 4.45, OR noninterval = 10.46) or having an HRA (OR PCCRC = 3.68, OR noninterval = 8.04). PCCRC risk and interval PCCRC risk were significantly associated with follow-up recommendations that did not correlate with American Gastroenterological Association surveillance guidelines (OR PCCRC = 3.30, OR interval = 4.85). Approximately 30% of PCCRCs could be attributed to endoscopic quality.
UNASSIGNED: Overall PCCRC risk and noninterval PCCRC risk were significantly associated with traditional CRC risk factors including precancerous polyps and HRA on the index colonoscopy. Interval PCCRC was not associated with these risk factors. Many PCCRCs can be attributed to endoscopic quality, and nonadherence to CRC surveillance guidelines may be a novel risk factor.

In order to explore the association between meat consumption and gastrointestinal/colorectal cancer (CRC) risk and to estimate the Israeli population attributable fraction (PAF), we conducted a collaborative historical cohort study using the individual participant data of seven nutritional studies from the past 6 decades. We included healthy adult men and women who underwent a nutritional interview. Dietary assessment data, using food-frequency or 24-h recall questionnaires, were harmonized. The study file was linked to the National Cancer and death registries. Among 27,754 participants, 1216 (4.4%) were diagnosed with gastrointestinal cancers and 839 (3.0%) with CRC by the end of 2016. Using meta-analysis methods applied to Cox proportional hazard models (adjusted for daily energy intake, sex, age, ethnic origin, education and smoking),100 g/day increments in beef, red meat and poultry consumption, and 50 g/day increment in processed meat consumption were associated with hazard ratios (HRs) and 95% confidence intervals of 1.46 (1.06-2.02), 1.15 (0.87-1.52), 1.06 (0.89-1.26), and 0.93 (0.76-1.12), respectively, for CRC. Similar results were obtained for gastrointestinal cancer, although red meat consumption reached statistical significance (HR = 1.27; 95%CI: 1.02-1.58). The PAFs associated with a reduction to a maximum of 50 g/day in the consumption of red meat were 2.7% (95%CI: -1.9 to 12.0) and 5.2% (0.3-13.9) for CRC and gastrointestinal cancers, respectively. Reduction of beef consumption to a maximum of 50 g/day will result in a CRC PAF reduction of 7.5% (0.7%-24.3%). While beef consumption was associated with gastrointestinal/CRC excess risk, poultry consumption was not. A substantial part of processed meat consumption in Israel is processed poultry, perhaps explaining the lack of association with CRC.

OBJECTIVE: This comprehensive investigation delved into the intricate causal interplay existing between cardiovascular-related plasma proteins and the susceptibility to colorectal cancer, leveraging the robust framework of Mendelian randomization, and employed expression profiling and survival analysis to unravel the latent clinical worth embedded within pertinent gene expressions.
METHODS: Protein quantitative trait loci (pQTLs) of 85 cardiovascular proteins were employed as instrumental variables to investigate the causal relationship between proteins and CRC risk using a Mendelian randomization approach. Causal inferences were graded as strong, intermediate or weak based on statistical checks. Drug-target MR examined VEGF receptors for their potential as therapeutic targets for colorectal cancer. Differential expression analysis, diagnostic ROC curves, and survival analyses were performed for identified proteins using RNA-seq data from The Cancer Genome Atlas (TCGA) colorectal cancer cohort.
RESULTS: Using cis-pQTLs, LOX-1, VEGF-A and OPG were associated with increased CRC risk (strong evidence), while PTX3, TNF-R2 and MMP-7 were protective (strong evidence). Pan-pQTL analysis found MMP-10 increased risk (intermediate evidence) and ADM increased risk (weak evidence). Drug-target MR found VEGF R1 may be promising therapeutic targets. Differential expression analysis revealed seven genes encoding the identified proteins were dysregulated in tumors. ROC analysis showed five gene expression had high diagnostic accuracy. KM analysis showed four genes had prognostic value.
CONCLUSIONS: This large-scale MR study implicates several cardiovascular proteins in CRC susceptibility and progression. Findings highlight roles for VEGF signaling and extracellular matrix regulation. Results nominate specific proteins as potential diagnostic biomarkers or therapeutic targets warranting further investigation.

BACKGROUND: Obesity may increase colorectal cancer (CRC) risk through mechanisms of increased inflammation. Although BMI is the most used adiposity indicator, it may less accurately measure adiposity in Black populations. Herein, we investigate associations between BMI, low albumin as an inflammation biomarker, and CRC risk in a racially diverse cohort.
METHODS: Participant data arise from 71,141 participants of the Southern Community Cohort Study, including 724 incident CRC cases. Within the cohort, 69% are Black. Blood serum albumin concentrations, from samples taken at enrollment, were available for 235 cases and 567 controls. Controls matched by age, sex, and race were selected through incidence density sampling. Cox proportional hazards calculated BMI and CRC risk associations (hazard ratios [HRs]; 95% confidence intervals [CIs]. Conditional logistic regression calculated albumin and CRC risk associations (odds ratios [ORs]; 95%CIs).
RESULTS: Underweight, but not overweight or obese, compared to normal BMI was associated with increased CRC risk (HR:1.75, 95%CI:1.00-3.09). Each standard deviation increase of albumin was associated with decreased CRC risk, particularly for those who self-identified as non-Hispanic Black (OR: 0.56, 95%CI:0.34-0.91), or female (OR:0.54, 95%CI:0.30-0.98), but there was no evidence for interaction by these variables (p-interactions > 0.05). Moreover, albumin concentration was lower in Black than White participants. Mediation analysis suggested that the relation between albumin and CRC was not mediated by BMI.
CONCLUSIONS: Null associations of overweight/obesity with CRC risk demonstrates limited utility of BMI, especially among Black populations. Low albumin may indicate CRC risk. In Black individuals, albumin may better predict adiposity related risks than BMI.

BACKGROUND: The -93G > A (rs1800734) polymorphism within the core promoter region of MLH1 gene is associated with MLH1 CpG island hypermethylation. This polymorphism has recently been proposed as a low penetrance variant for colorectal cancer. Many published studies have evaluated the association between the MLH1 -93G > A polymorphism and colorectal cancer risk. However, the results remain conflicting rather than conclusive. The aim of this study was to assess the association between the MLH1 -93G > A polymorphism and the risk of colorectal cancer in patients with colorectal cancer in the lower northeastern region of Thailand.
METHODS: One hundred fifty one samples from colorectal cancer patients and 100 samples from healthy control group were analyzed. Genomic DNA was extracted from white blood cell of all samples. The real-time polymerase chain reaction (qPCR) was used to demonstrate genetic polymorphism of MLH1 rs1800734.
RESULTS: This study demonstrated that the frequency of MLH1 rs1800734 in patients with colorectal cancer was higher than healthy control group. The MLH1 rs1800734 polymorphism variant AA was associated with an increased risk of colorectal cancer (p < 0.05). The MLH1 polymorphism variant AA carriers presented 1.36-folds high risk of colorectal cancer and the alcohol consumption was linked to their likelihood of developing colorectal cancer and their tumor\'s grade.
CONCLUSIONS: This study showed that MLH1 rs1800734 genotype AA was associated with colorectal cancer risk in the lower northeastern region of Thailand.

Numerous demographic factors have been associated with colorectal cancer (CRC) risk. To better define biological mechanisms underlying these associations, we performed RNA sequencing of stem-cell-enriched organoids derived from the healthy colons of seven European Americans and eight African Americans. A weighted gene co-expression network analysis was performed following RNA sequencing. Module-trait relationships were determined through the association testing of each module and five CRC risk factors (age, body mass index, sex, smoking history, and race). Only modules that displayed a significantly positive correlation for gene significance and module membership were considered for further investigation. In total, 16 modules were associated with known CRC risk factors (p < 0.05). To contextualize the role of risk modules in CRC, publicly available RNA-sequencing data from TCGA-COAD were downloaded and re-analyzed. Differentially expressed genes identified between tumors and matched normal-adjacent tissue were overlaid across each module. Loci derived from CRC genome-wide association studies were additionally overlaid across modules to identify robust putative targets of risk. Among them, MYBL2 and RXRA represented strong plausible drivers through which cigarette smoking and BMI potentially modulated CRC risk, respectively. In summary, our findings highlight the potential of the colon organoid system in identifying novel CRC risk mechanisms in an ancestrally diverse and cellularly relevant population.

Obesity-mediated inflammation represents a key connection between the intake of foods with high inflammatory potential and colorectal cancer (CRC) risk. We aimed to explore the association between energy-adjusted dietary inflammatory index (E-DII) in relation to CRC risk in both obese and non-obese subjects. This study included 99 histopathologically confirmed CRC cases, 73 colonic polyps cases, and 141 healthy controls from tertiary medical centres in both urban and suburban areas in Peninsular Malaysia. The subjects were categorised into body mass index (BMI) < 25 kg/m2 and BMI ≥ 25 kg/m2 groups. E-DII scores were computed based on dietary intake assessed using a validated food frequency questionnaire (FFQ). Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for potential cofounders. The mean dietary energy intake and mean BMI values of the subjects tended to increase as the E-DII scores increased (p for trend < 0.001). E-DII was significantly related to CRC risk only in obese subjects (OR = 1.45; 95% CI = 1.30-1.77; p < 0.001 for trend). Stratified analyses of risk factors showed significant associations between E-DII and CRC risk by age group (p for interaction = 0.030), smoking status (p for interaction = 0.043), and anthropometric indices for both males and females (p for interaction < 0.001) in the most pro-inflammatory E-DII quartile vs. the lowest E-DII quartile. Overall, pro-inflammatory diets were associated with an increased incidence of CRC in the Malaysian population, particularly in obese subjects.

OBJECTIVE: The high-meat, low-fibre Western diet is strongly associated with colorectal cancer risk. Mycoprotein, produced from Fusarium venanatum, has been sold as a high-fibre alternative to meat for decades. Hitherto, the effects of mycoprotein in the human bowel have not been well considered. Here, we explored the effects of replacing a high red and processed meat intake with mycoprotein on markers of intestinal genotoxicity and gut health.
METHODS: Mycomeat (clinicaltrials.gov NCT03944421) was an investigator-blind, randomised, crossover dietary intervention trial. Twenty healthy male adults were randomised to consume 240 g day-1 red and processed meat for 2 weeks, with crossover to 2 weeks 240 g day-1 mycoprotein, separated by a 4-week washout period. Primary end points were faecal genotoxicity and genotoxins, while secondary end points comprised changes in gut microbiome composition and activity.
RESULTS: The meat diet increased faecal genotoxicity and nitroso compound excretion, whereas the weight-matched consumption of mycoprotein decreased faecal genotoxicity and nitroso compounds. In addition, meat intake increased the abundance of Oscillobacter and Alistipes, whereas mycoprotein consumption increased Lactobacilli, Roseburia and Akkermansia, as well as the excretion of short chain fatty acids.
CONCLUSIONS: Replacing red and processed meat with the Fusarium-based meat alternative, mycoprotein, significantly reduces faecal genotoxicity and genotoxin excretion and increases the abundance of microbial genera with putative health benefits in the gut. This work demonstrates that mycoprotein may be a beneficial alternative to meat within the context of gut health and colorectal cancer prevention.

Obesity is considered a risk factor for different types of cancer, including colorectal cancer (CRC). Bariatric surgery has been associated with improvements in obesity-related co-morbidities and reductions in overall cancer risk. However, given the contradictory outcomes of several cohort studies, the impact of bariatric surgery on CRC risk appears controversial. Furthermore, measurement of CRC biomarkers following Roux-en-Y gastric bypass (RYGB) has revealed hyperproliferation and increased pro-inflammatory gene expression in the rectal mucosa. The proposed mechanisms leading to increased CRC risk are alterations of the gut microbiota and exposure of the colorectum to high concentrations of bile acids, both of which are caused by RYGB-induced anatomical rearrangements. Studies in animals and humans have highlighted the similarities between RYGB-induced microbial profiles and the gut microbiota documented in CRC. Microbial alterations common to post-RYGB cases and CRC include the enrichment of pro-inflammatory microbes and reduction in butyrate-producing bacteria. Lower concentrations of butyrate following RYGB may also contribute to an increased risk of CRC, given the anti-inflammatory and anticarcinogenic properties of this molecule. Laparoscopic sleeve gastrectomy appears to have a more moderate impact than RYGB; however, relatively few animal and human studies have investigated its effects on CRC risk. Moreover, evidence regarding the impact of anastomosis gastric bypass on one is even more limited. Therefore, further studies are required to establish whether the potential increase in CRC risk is restricted to RYGB or may also be associated with other bariatric procedures.

Dietary fiber or non-starch polysaccharides (NSP) may provide protection from CRC development. Epidemiologic studies on the association between dietary fiber and CRC is inconsistent are limited on NSP as a modifiable risk factor. Using the Singapore Chinese Health Study, a population-based prospective cohort of 61,321 cancer-free middle-aged or older Chinese Singaporeans, we examined the association between dietary fiber and NSP intakes and CRC risk. Fiber and NSP intakes at baseline were obtained using a validated semi-quantitative food frequency questionnaire coupled with the Singapore Food Composition Database. Cox proportional hazard regression model was used to estimate the hazard ratios (HRs) and respective 95% confidence intervals (CIs) for CRC associated with dietary fiber and NSP intakes after adjusting for potential confounders. After an average of 17.5 years of follow-up, 2,140 participants developed CRC. NSP was inversely associated with the risk of CRC in a dose-dependent manner whereas dietary fiber was not associated with risk of CRC overall or histologic subtypes. The multivariable-adjusted HRs (95% CIs) of CRC for quartiles 2, 3 and 4 of dietary NSP intake were 0.99 (0.88-1.11), 0.98 (0.87-1.11) and 0.84 (0.73-0.95), respectively, compared with the lowest quartile (P trend =0.006). This inverse association was more apparent for colon cancer (HRQ4 vs. Q1=0.79, 95% CI: 0.67-0.93, P trend =0.003) than rectal cancer (HR Q4 vs. Q1=0.92, 95% CI: 0.74-1.13, P trend =0.53). Our findings suggested that dietary NSP but not fiber is associated with a reduced risk of colon cancer in Chinese Singaporeans.
Non-starch polysaccharides may be beneficial for colorectal cancer primary prevention.