Decreased Risk Of Colorectal Cancer Research Articles

Optimal glycaemic control and the reduced risk of colorectal adenoma and cancer in patients with diabetes: a population-based cohort study

ObjectiveWhether varying degrees of glycaemic control impact colonic neoplasm risk in patients with diabetes mellitus (DM) remains uncertain.DesignPatients with newly diagnosed DM were retrieved from 2005 to 2013. Optimal glycaemic...

The Association of Low-Carbohydrate Diet and HECTD4 rs11066280 Polymorphism with Risk of Colorectal Cancer: A Case-Control Study in Korea

BackgroundGlucose is a main source of energy for tumor cells. Thus, a low-carbohydrate diet (LCD) is thought to make a significant contribution to cancer prevention. In addition, LCD and HECT domain E3 ubiquitin protein ligase 4 (HECTD4) gene may be related to insulin resistance. ObjectivesWe explored whether LCD score and HECTD4 rs11066280 are etiological factors for colorectal cancer (CRC) and whether LCD score interacts with HECTD4 rs11066280 to modify CRC risk. MethodsWe included 1457 controls and 1062 cases in a case-control study. The LCD score was computed based on the proportion of energy obtained from carbohydrate, protein, and fat, as determined by a semiquantitative food frequency questionnaire. We used unconditional logistic regression models to explore the association of HECTD4 with CRC prevention and interaction of LCD score and HECTD4 polymorphism with CRC preventability. ResultsIndividuals with AA/AT genotypes who carried a minor allele (A) of HECTD4 rs11066280 exhibited a decreased CRC risk [odds ratio (OR) = 0.75, 95% confidence interval (CI): 0.62, 0.91]. In addition, a protective effect of high LCD score against CRC development was identified (OR = 0.52, 95% CI: 0.40, 0.68, P for trend <0.001). However, the effect of LCD depended on individual’s genetic background, which appears only in participants with TT genotype of HECTD4 rs11066280 [OR = 0.49 (0.36–0.68), P interaction = 0.044]. ConclusionsOur findings suggest a protective effect of LCD and a minor allele of HECTD4 rs11066280 against CRC development. In addition, we provide an understanding of the interaction effect of LCD and HECTD4 rs11066280 on CRC, which may be helpful for establishing diet plans regarding cancer prevention.

Dietary patterns, untargeted metabolite profiles and their association with colorectal cancer risk

We investigated data-driven and hypothesis-driven dietary patterns and their association to plasma metabolite profiles and subsequent colorectal cancer (CRC) risk in 680 CRC cases and individually matched controls. Dietary patterns were identified from combined exploratory/confirmatory factor analysis. We assessed association to LC–MS metabolic profiles by random forest regression and to CRC risk by multivariable conditional logistic regression. Principal component analysis was used on metabolite features selected to reflect dietary exposures. Component scores were associated to CRC risk and dietary exposures using partial Spearman correlation. We identified 12 data-driven dietary patterns, of which a breakfast food pattern showed an inverse association with CRC risk (OR per standard deviation increase 0.89, 95% CI 0.80–1.00, p = 0.04). This pattern was also inversely associated with risk of distal colon cancer (0.75, 0.61–0.96, p = 0.01) and was more pronounced in women (0.69, 0.49–0.96, p = 0.03). Associations between meat, fast-food, fruit soup/rice patterns and CRC risk were modified by tumor location in women. Alcohol as well as fruit and vegetables associated with metabolite profiles (Q2 0.22 and 0.26, respectively). One metabolite reflecting alcohol intake associated with increased CRC risk, whereas three metabolites reflecting fiber, wholegrain, and fruit and vegetables associated with decreased CRC risk.

Genetic association of circulating interleukins and risk of colorectal cancer: A bidirectional Mendelian randomization study.

Previous studies have reported that inflammation, especially interleukin family members, plays an important role in the development of colorectal cancer (CRC). However, because of various confounders and the lack of clinical randomized controlled trial, the causal relationship between genetically predicted level of interleukin family and CRC risk has not been fully explained. Bi-directional Mendelian randomization (MR) was conducted to investigate the causal association between interleukin family members and CRC. Several genetic variables were extracted as instrumental variables (IVs) from summary data of genome-wide association studies (GWAS) for interleukin and CRC. IVs of interleukin family were obtained from recently published GWAS studies and the summary data of CRC was from FinnGen Biobank. After a series of quality control measures and strict screening, six models were used to evaluate the causal relationship. Pleiotropy, heterogeneity test, and a variety of sensitivity analysis were also used to estimate the robustness of the model results. Genetically predicted higher circulating levels of IL-2 (odds ratio [OR]: 0.76; 95% confidence interval [CI]: 0.63-0.92; p = .0043), IL-17F(OR: 0.78; 95% CI: 0.62-1.00; p = .015), and IL-31 (OR: 0.88; 95% CI: 0.79-0.98; p = .023) were suggestively associated with decreased CRC risk. However, higher level of IL-10 (OR: 1.40; 95% CI: 1.18-1.65; p = .000094) was causally associated with increased risk of CRC. Reverse MR results indicated that the exposure of CRC was suggestively associated with higher levels of IL-36α (OR: 1.23; 95% CI: 1.01-1.49; p = .040) and IL-17RD (OR: 1.22; 95% CI, 1.00-1.48; p = .048) and lower level of IL-13 (OR: 0.78; 95% CI: 0.65-0.95; p = .013). The overall MR results did not provide evidence for causal relationships between other interleukins and CRC (p > .05). We offer suggestive evidence supporting a potential causal relationship between circulating interleukins and CRC, underscoring the significance of targeting circulating interleukins as a strategy to mitigate the incidence of CRC.

Partial substitution of red or processed meat with plant-based foods and colorectal cancer risk

Abstract Background Consumption of plant-based foods, particularly whole grains, may decrease colorectal cancer (CRC) risk, while red and processed meat consumption increases it. Moreover, shifting to more plant-based diets promotes sustainable food systems. Yet, few studies have examined the impact of dietary shifts towards more plant-based diets on CRC risk. We modelled a partial substitution of red or processed meat with whole grains, vegetables or fruits in relation to CRC risk in Finnish adults. Methods Our data comprised 43 788 participants (79% men) aged ≥25 years from five Finnish cohorts. The median follow-up was 29 years, during which 1124 CRC cases were diagnosed. Diet was assessed by a validated food frequency questionnaire. We modelled substitutions of 100g/week of red meat or 50g/week of processed meat with an equivalent amount of plant-based foods. In a two-stage meta-analysis, cohort-specific hazard ratios (HR) were calculated using Cox proportional hazards model and pooled together. We adjusted the analyses for sex and other relevant confounders. Results We observed a small decrease in CRC risk when red or processed meat was partially substituted with vegetables (red meat: HR 0.97, 95% CI 0.94-0.99, P = 0.008; processed meat: 0.99, 0.98-1.00, P = 0.029) or fruits (red meat: 0.97, 0.94-0.99, P = 0.007; processed meat: 0.99, 0.98-1.00, P = 0.036). No association occurred between the partial substitution of red or processed meat with whole grains and CRC risk. Conclusions Our results suggested that already small and easily implemented substitutions of red or processed meat with vegetables or fruits could reduce CRC risk in Finnish adults. The findings highlight the need for effective nutrition policy actions to promote the shift towards more plant-based diets that would benefit both public health and sustainable food systems. Further research on similar substitutions in relation to CRC risk is required in different populations and real-life settings. Key messages • Already small and easily implemented substitutions of 100g/week of red meat or 50g/week of processed meat with vegetables or fruits could reduce colorectal cancer risk in Finnish adults. • The findings highlight the need for effective nutrition policy actions to promote the shift towards more plant-based diets that would benefit both public health and the sustainability of food systems.

Prioritization of risk genes in colorectal cancer by integrative analysis of multi-omics data and gene networks.

Genome-wide association studies (GWASs) have identified over 140 colorectal cancer (CRC)-associated loci; however, target genes at the majority of loci and underlying molecular mechanisms are poorly understood. Here, we utilized a Bayesian approach, integrative risk gene selector (iRIGS), to prioritize risk genes at CRC GWAS loci by integrating multi-omics data. As a result, a total of 105 high-confidence risk genes (HRGs) were identified, which exhibited strong gene dependencies for CRC and enrichment in the biological processes implicated in CRC. Among the 105 HRGs, CEBPB, located at the 20q13.13 locus, acted as a transcription factor playing critical roles in cancer. Our subsequent assays indicated the tumor promoter function of CEBPB that facilitated CRC cell proliferation by regulating multiple oncogenic pathways such as MAPK, PI3K-Akt, and Ras signaling. Next, by integrating a fine-mapping analysis and three independent case-control studies in Chinese populations consisting of 8,039 cases and 12,775 controls, we elucidated that rs1810503, a putative functional variant regulating CEBPB, was associated with CRC risk (OR=0.90, 95%CI=0.86-0.93, P=1.07×10-7). The association between rs1810503 and CRC risk was further validated in three additional multi-ancestry populations consisting of 24,254 cases and 58,741 controls. Mechanistically, the rs1810503 A to T allele change weakened the enhancer activity in an allele-specific manner to decrease CEBPB expression via long-range promoter-enhancer interactions, mediated by the transcription factor, REST, and thus decreased CRC risk. In summary, our study provides a genetic resource and a generalizable strategy for CRC etiology investigation, and highlights the biological implications of CEBPB in CRC tumorigenesis, shedding new light on the etiology of CRC.

Associations of Albumin and BMI with Colorectal Cancer Risk in the Southern Community Cohort Study: a Prospective Cohort Study.

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. 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). 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. 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.

Genome-wide interaction analysis of folate for colorectal cancer risk

BackgroundEpidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate’s role in CRC. ObjectivesOur aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk. MethodsWe applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO). ResultsInverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10-8) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate. ConclusionsVariation in 3p25.2 locus may modify the association of folate supplement with CRC risk. Experimental studies and studies incorporating other relevant omics data are warranted to validate this finding.

Dissecting the pathogenic effects of smoking and its hallmarks in blood DNA methylation on colorectal cancer risk.

Tobacco smoking is suggested as a risk factor for colorectal cancer (CRC), but the complex relationship and the potential pathway are not fully understood. We performed two-sample Mendelian randomisation (MR) analyses with genetic instruments for smoking behaviours and related DNA methylation in blood and summary-level GWAS data of colorectal cancer to disentangle the relationship. Colocalization analyses and prospective gene-environment interaction analyses were also conducted as replication. Convincing evidence was identified for the pathogenic effect of smoking initiation on CRC risk and suggestive evidence was observed for the protective effect of smoking cessation in the univariable MR analyses. Multivariable MR analysis revealed that these associations were independent of other smoking phenotypes and alcohol drinking. Genetically predicted methylation at CpG site cg17823346 [ZMIZ1] were identified to decrease CRC risk; while genetically predicted methylation at cg02149899 would increase CRC risk. Colocalization and gene-environment interaction analyses added further evidence to the relationship between epigenetic modification at cg17823346 [ZMIZ1] as well as cg02149899 and CRC risk. Our study confirms the significant association between tobacco smoking, DNA methylation and CRC risk and yields a novel insight into the pathogenic effect of tobacco smoking on CRC risk.

Association between nutrient intake related to the one-carbon metabolism and colorectal cancer risk: a case–control study in the Basque Country

PurposeEpidemiologic evidence for the association between methyl-donor nutrient intake and colorectal cancer (CRC) risk remains inconclusive. We aimed to examine the relationship between intake of vitamins of the B group, methionine, total choline and betaine and CRC risk, in a population from the CRC screening programme in the Basque Country.DesignThis observational study included 308 patients with CRC and 308 age- and sex-matched subjects as controls. During recruitment, dietary, anthropometric, lifestyle, socioeconomic, demographic, and health status information was collected. Conditional logistic regression was used to estimate the odds ratios (ORs) for CRC risk.ResultsThe adjusted ORs for CRC risk decreased with higher intakes of choline and betaine (p < 0.05). After further adjustment for folate, high intake of choline and betaine remained associated with a reduced CRC risk (adjusted model for choline, OR third tertile vs first tertile = 0.45, 95% CI 0.26–0.80, p = 0.006; for betaine, OR third tertile vs first tertile = 0.27, 95% CI 0.16–0.47, p < 0.001). Regarding the other nutrients, our findings indicated a non-significant decrease in CRC risk with the high level of intake.ConclusionsOur data suggest that choline and betaine intake influence CRC risk in the studied population.

Dietary Choline and Betaine Intake and Risk of Colorectal Cancer in an Iranian Population.

Colorectal cancer (CRC) is increasing in low- and middle-income countries, likely due to changing lifestyle habits, including diet. We aimed to investigate the relationship between dietary betaine, choline, and choline-containing compounds and CRC risk. We analyzed data from a case-control study, including 865 CRC cases and 3206 controls from Iran. Detailed information was collected by trained interviewers using validated questionnaires. The intake of free choline, phosphocholine (Pcho), glycerophosphocholine (GPC), phosphatidylcholine (PtdCho), and sphingomyelin (SM), as well as of betaine was estimated from food frequency questionnaires and categorized into quartiles. The odds ratios (OR) and 95% confidence intervals (CI) of CRC for choline and betaine quartiles were calculated using multivariate logistic regression by adjusting for potential confounders. We observed excess risk of CRC in the highest versus lowest intake of total choline (OR = 1.23, 95% CI 1.13, 1.33), GPC (OR = 1.13, 95% CI 1.00, 1.27), and SM (OR = 1.14, 95% CI 1.01, 1.28). The intake of betaine exerted an inverse association with CRC risk (OR = 0.91, 95% CI 0.83, 0.99). There was no association between free choline, Pcho, PtdCho, and CRC. Analyses stratified by gender showed an elevated OR of CRC in men for SM intake OR = 1.20, 95% CI 1.03, 1.40) and a significantly decreased CRC risk in women for betaine intake (OR = 0.84, 95% CI 0.73, 0.97). Dietary modifications leading to an increase in betaine sources and managing the use of animal products as references for SM or other choline types might contribute to decreasing the risk of CRC.

Association of vitamin D receptor polymorphisms with colorectal cancer susceptibility: A systematic meta-analysis

Recent studies have reported an association between vitamin D receptor (VDR) polymorphisms and colorectal cancer (CRC) risk; however, the results are controversial. This meta-analysis was performed to investigate whether the Cdx-2, Tru9I, FokI, BsmI, TaqI, and ApaI polymorphisms were correlated with CRC susceptibility. All potential studies were retrieved by searching the PubMed, EMBASE, and Cochrane Library databases through October 2, 2021. Odds ratios (ORs) with 95% confidence intervals were used to evaluate the correlation between VDR gene Cdx-2, Tru9I, FokI, BsmI, TaqI, and ApaI polymorphisms and CRC risk. In this meta-analysis, the BsmI variant was significantly correlated with a lower risk of CRC, especially in Caucasian population (B vs b: OR 0.94, 95%CI 0.90-0.99; BB vs bb: OR 0.88; 95%CI 0.79-0.97; BB vs Bb/bb: BB vs Bb/bb: OR 0.89; 95%CI 0.81-0.98). A statistically significant result from the FokI polymorphism was observed in colon cancer rather than rectal cancer (Ff vs FF: OR 0.86, 95%CI 0.84-0.93; ff/Ff vs FF: OR 0.88, 95%CI 0.79-0.98; ff vs Ff/FF: OR 0.90, 95%CI 0.82-0.99). Similarly, Cdx-2 polymorphism was found to be associated with decreased CRC risk among Africans (C vs c: OR 0.50, 95%CI 0.33-0.75; CC vs cc: OR 0.09, 95%CI 0.01-0.77; Cc vs cc: OR 0.49, 95%CI 0.30-0.81; CC/Cc vs cc: OR 0.45, 95%CI 0.28-0.74,). Our findings indicate that VDR polymorphisms are significantly associated with CRC risk.

Garlic consumption and colorectal cancer risk in US adults: a large prospective cohort study.

To clarify the inconsistent findings of epidemiological studies on the association between dietary garlic consumption and colorectal cancer (CRC) incidence, by prospectively assessing the association in a large US population. Data of 58,508 participants (aged 55-74) from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial were analyzed. Dietary data were collected using a validated questionnaire. Multivariable Cox regression analysis determined hazard ratio (HR) and 95% confidence interval (CI). Restricted cubic spline regression was used to investigate the non-linear relationship, and subgroup analysis was conducted to examine potential effect modifiers. During a median follow-up of 12.05 years, 782 CRC cases were documented, including 456 proximal colon cancer cases, 322 distal CRC cases, and 4 CRC cases with an unknown site. Moderate dietary garlic consumption was significantly associated with a reduced risk of overall CRC (HRquintile 3vs. 1: 0.70, 95% CI: 0.54 to 0.91, p = 0.007, P for trend: 0.434), exhibiting a U-shaped dose-response pattern, and also with overall CRC in males in the stratified Cox regression model (Model 2: HRquintile 3vs. 1: 0.57, 95% CI: 0.40 to 0.81, p = 0.002), but not in females. The protective association was more pronounced in men, Caucasian, and those with lower alcohol consumption. Notably, these protective effects were observed for overall distal CRC (HRquintile 3vs. 1: 0.62, 95% CI: 0.42 to 0.93, p = 0.021; and HRquintile 4vs. 1: 0.63, 95% CI: 0.43 to 0.92, p = 0.018, P for trend: 0.208); and for distal CRC in males (HRquintile 3vs. 1: 0.40, 95% CI: 0.22 to 0.71, p = 0.002, P for trend: 0.696), but not for proximal CRC. Moderate consumption of dietary garlic is associated with a decreased CRC risk in the US population, with variations based on CRC anatomic subsites. Further in-depth prospective studies are needed to validate these findings in different populations and to explore subsites-specific associations.

Role of Dairy Foods, Fish, White Meat, and Eggs in the Prevention of Colorectal Cancer: A Systematic Review of Observational Studies in 2018-2022.

There is limited evidence to support the relationship between the consumption of animal-source foods other than red meat and processed meat and colorectal cancer (CRC) risk. We aimed to examine the recent available evidence from observational studies about the association between these food groups’ intake and CRC risk. For this systematic review, we searched the PubMed database for the last five years. A total of fourteen cohort studies and seven case–control studies comprising a total of >60,000 cases were included. The studies showed a consistent significant decrease in CRC risk, overall and by subsites, associated with a high consumption of total dairy products. Less strong effects associated with the consumption of any subtype of dairy product were observed. Fish consumption, overall and by subtypes (oily or non-oily and fresh or canned), showed a mild inverse association with CRC risk. The association between white meat and egg intake and CRC risk was low and based on a small number of studies; thus, these findings should be interpreted with caution. In conclusion, a high consumption of total dairy products was associated with a lower CRC risk. However, evidence for fish, white meat, and eggs and the CRC risk were not as strong.

Colorectal Cancer Risk Is Impacted by Sex and Type of Surgery After Bariatric Surgery.

Sex differences exist in the associations between obesity and the risk of colorectal cancer (CRC). However, limited data exist on how sex affects CRC risk after bariatric surgery. This retrospective cohort study used the 2012-2020 MarketScan database. We employed a propensity-score-matched analysis and precise coding to define CRC in this nationwide US study. Adjusted hazards ratio (HR) assessed CRC risk ≥ 6months. In a restricted analysis, logistic regression with adjusted odds ratios (OR) examined CRC risk ≥ 3years. Our sample included 327,734 controls with severe obesity and 88,630 patients with Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (VSG). The odds of cessation of diabetes mellitus medications, a surrogate for diabetes remission, were higher post-surgery vs. controls, especially in RYGB and males. In females, CRC risk decreased post-RYGB compared to controls (HR = 0.40, 95%CI: 0.18-0.87, p = 0.02). However, VSG was not associated with lower CRC risk in females. Paradoxically, in males compared to controls, CRC risk trended toward an almost significant increase, especially after 3years or more from surgery (OR = 2.18, 95%CI: 0.97-4.89, p = 0.06). Males had a higher risk of CRC, particularly rectosigmoid cancer, than females after bariatric surgery (HR = 2.69, 95% CI: 1.35-5.38, p < 0.001). Furthermore, diabetes remission was not associated with a lower CRC risk post-surgery. Our data suggest an increased risk of CRC in males compared to females after bariatric surgery. Compared to controls, there was a decrease in CRC risk in females' post-RYGB but not VSG. Mechanistic studies are needed to explain these differences.

Contribution of 5-Methyltetrahydrofolate-Homocysteine Methyltransferase Reductase Genotypes to Colorectal Cancer in Taiwan.

5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) is responsible for folate metabolism, and we aimed to investigate its genetic role in colorectal cancer (CRC) among Taiwanese. A total of 362 cases and 362 controls were recruited and their MTRR rs1801394 (A66G) and rs1532268 (C524T) genotypes were examined. The behavioral factors and clinicalpathological factors were also analyzed. MTRR rs1801394 genotypes were associated with CRC risk (p for trend=0.0087). In detail, G/G genotype was associated with lower risk (p=0.0049, OR=0.39, 95%CI=0.20-0.76). As for allelic frequency analysis, G allele was also associated with decreased CRC risk (p=0.0026, OR=0.68, 95%CI=0.53-0.88). There was no significant association as for MTRR rs1532268. Among non-smokers and non-alcohol drinkers, those with G/G genotype were at 0.38- and 0.46-fold odds of having CRC. There were no significant protective effects among smokers or alcohol drinkers. MTRR rs1801394 GG genotype can be a protective marker for CRC risk in Taiwan.

Association between long noncoding RNA rs944289 and rs7990916 polymorphisms and the risk of colorectal cancer in a Chinese population

Long non-coding RNAs (LncRNAs) play vital roles in the tumorigenesis of many cancers. Single nucleotide polymorphisms (SNPs) of the lncRNA also play vital roles in tumorigenesis. We explored lncRNA rs944289 and rs7990916 polymorphisms and analyzed the relationship between these lncRNA polymorphisms with the colorectal cancer (CRC) risk in a Chinese population. We recruited 1003 CRC patients from the Affiliated People’s Hospital of Jiangsu University and the Fujian Medical University Union Hospital from October 2014 to August 2017. Genomic DNA was extracted using a DNA Kit from lymphocytes of peripheral blood and the genotyping was performed with a SNPscan method. We found that the rs944289 TT homozygote was associated with the decreased CRC risk in the overall population. LncRNA rs944289 TT decreased the CRC risk in the subgroup of female, male, age ≥ 61, without alcohol intake, smoking and BMI ≥ 24 by logistic regression. The subgroup analysis revealed that lncRNA rs7990916 was not associated with CRC risk except for age < 61. Logistic regression analysis revealed that lncRNA rs944289 TT homozygote was associated with the increased risk of rectum cancer (TT vs. CC + CT: adjusted OR = 1.29, 95% CI 1.10–1.66, P = 0.041) or colon cancer. In summary, we proved that lncRNA rs944289 might be significantly related to the decreased CRC risk in the Chinese Han populations and lncRNA rs7990916 was not associated with the CRC risk except for patients of age < 61. In the future, studies with larger samples should be conducted to validate our results.

Higher Yogurt Consumption Is Associated With Lower Risk of Colorectal Cancer: A Systematic Review and Meta-Analysis of Observational Studies

Background: Yogurt is known to be nutrient-rich and probiotic content, which gather optimism due to their potential role in preventing and managing cancers. The effect of yogurt consumption on colorectal cancer (CRC) is inconsistent.Objective: This study aims to investigate the association of yogurt consumption with the risk of CRC.Methods: Three databases, namely, PubMed, Web of Science, and Embase, were searched for all relevant studies from July 2021 on the association of yogurt consumption with CRC risk. We pooled the odds ratios (ORs) and their 95% CIs using a random-effects meta-analysis to assess the association.Results: Finally, 16 studies met the inclusion criteria and were chosen in the meta-analysis. Yogurt consumption was significant with lower risk of CRC risk in the overall comparison (OR = 0.87, 95% CI: 0.81–0.94), in the cohort studies (OR = 0.91, 95% CI: 0.86–0.97), and case-control studies (OR = 0.75, 95% CI: 0.65–0.85). With regard to subgroup analyses by study region, cancer type, publication year, and sex, yogurt consumption significantly decreased overall CRC, colon cancer, and distal colon cancer risks. In stratified analyses, we observed significantly decreased CRC risk in Europe and Africa and published after 2010 and overall population. Sensitivity analysis indicated the result is stable and there is no publication bias in the meta-analysis.Conclusions: Overall, this study indicated that yogurt intake was related to a decreased risk of CRC.

RECK Variants are Associated with Clinicopathological Features and Decreased Susceptibility in Mexican Patients with Colorectal Cancer.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of death worldwide. Down-regulation of the cysteine-rich reversion-inducing protein with Kazal motifs (RECK) has been confirmed in numerous human cancers and is clinically associated with metastasis. This study aims to explore, for the first time, the possible association of the RECK variants rs11788747 and rs10972727 with CRC susceptibility and clinicopathological features. DNA from 130 CRC patients and 130 healthy blood donors was analyzed. Identification of genetic variants was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated using the odds ratio (OR) test and P values were adjusted using the Bonferroni test. Individuals carrying the G/G genotype for the rs11788747 variant showed a lower risk of colorectal cancer (OR 0.33; 95% CI 0.16-0.70; P = 0.006). Patients older than 50 years who carry the G/G genotype have a lower risk of CRC (OR 0.26; 95% CI 0.09-0.73; P = 0.019) and of developing advanced tumor-nodule-metastasis (TNM) stages (OR 0.23; 95% CI 0.09-0.54; P = 0.001). Individuals carrying the A/A genotype of the rs10972727 variant also showed decreased risk of CRC (OR 0.38; 95% CI 0.19-0.77; P = 0.011), and were associated with age (over 50 years), sex, advanced TNM stages, and tumor location in the colon. Our results suggest that the RECK variants studied here (rs11788747 and rs10972727) are associated with decreased CRC risk, TNM stages and tumor location.

S955 Differential Risk of Colorectal Cancer in Inflammatory Bowel Disease Patients Treated With Advanced Therapies, Immunomodulators, and 5-Aminosalicylates: A Multi-Research Network Study Utilizing the TrinetX Database

Introduction: Colonic inflammation is an established risk factor for Colorectal Cancer (CRC) in IBD. The decrease in CRC risk by modulating underlying inflammation with different mechanistic forms of medical therapy is unclear. We hypothesized that advanced therapy for IBD is chemoprotective. We compared the rates of CRC in patients on different classes of medications. Methods: Clinical data was compiled from the TriNetX database, accessed on April, 14, 2021. TriNetX is a globally federated research network, that provides clinical information from 51 HCOs in the US. Patients with reported ICD-10 codes of K50 (Crohn’s Disease, CD) and K51 (Ulcerative Colitis, UC) from 2005-21, were included. Patients were subdivided into 6 cohorts within each form of IBD (CD, UC), categorized by therapy type: 5-aminosalicylic acid (5-ASA), anti-TNFs (IFX, ADA, GOL, CZP), Immunomodulators (AZA, 6-MP, MTX), tofacitinib (TOF), ustekinumab (USK) and Vedolizumab (VEDO). We evaluated demographics, CRC risk factors, inflammatory markers, IBD-related surgery, behavior and extent. The primary outcome of interest was diagnosis of CRC at least 3 month from therapy initiation. For continuous data, analyses were conducted using independent t-tests. For categorical data, analyses were conducted using chi-square tests. All tests were two-tailed with α=.05. Results: At the time of data collection, 35,243 patients were on therapy for CD and 39,223 patients were on therapy for UC. In the CD cohort, majority of the patients were on 5-ASAs (47.3%) followed by anti-TNFs (28.2%), immunomodulators (18%), USK (3.8%) and VEDO (2.7%). Incidence of CRC at least 3 months after initiation of therapy was lowest for anti-TNFs and USK at 0.45% and 0.44%; followed by VEDO at 0.73% and immunomodulators at 1.03%; and highest for 5-ASA at 1.24%. In the UC cohort, the majority of the patients were on 5-ASAs (86%) followed by immunomodulators (6.3%), anti-TNFs (5.4%), VEDO (1.5%), TOF (0.4%) and USK (0.3%). Incidence of CRC at least 3 months after initiation of therapy was lowest for USK at 0%, followed by VEDO (0.82%), anti-TNFs (0.85%), 5-ASA (1.21%), immunomodulators (1.66%) and TOF at 2.11%. The limitation of the study are small sample size for certain treatments and limited information on IBD phenotypes and disease behavior. Conclusion: In this multi-network database study, the incidence of CRC among CD was lowest for patients on anti-TNFs and highest for patients on 5-ASAs. For UC, incidence of CRC was lowest for patients on biologic therapies.Table 1.: Incidence of Colorectal Cancer (CRC) after at least 3 months of initiation of medication therapy