Prevention Of Colorectal Cancer Research Articles

Abstract B045: Colorectal cancer screening education intervention for Chamoru and Filipinos in Guam and Hawai‘i: Recommendations for culturally and age relevant education

Abstract Background. Pacific Islanders and Filipinos have low rates of colorectal cancer (CRC) screening. Filipinos in the US territory of Guam and the state of Hawai‘i comprise one of the largest ethnic racial groups in these locations, and CHamoru (Chamorro) in Guam constitute a majority of the population. The CRC age-adjusted mortality rate in Guam (17.3) is higher than the overall US (14.2) with a high rate among CHamoru (23.2). In Guam 45.6% of persons aged 45 and above have met USPSTF screening standards while in Hawai‘i Filipinos have the lowest CRC screening rates (69.9%) among Asian and Pacific Islander ethnic subgroups. Interventions to increase CRC screening in these populations are limited. This study explores recommendations for culturally relevant components of a CRC screening education intervention for CHamoru and Filipinos in Guam and Hawai‘i aged 40 and above. Methods. Qualitative methods employed focus groups (FG) and key informant interviews (KII) to facilitate storytelling, creating a familiar and safe space for knowledge, cultural beliefs, and screening education recommendations. Respective community councils advised on the study. A common FG and KII semi-structure guide was implemented. Purposive and snowball sampling was utilized. FGs were age and gender specific, e.g., men in their 40s, women aged 50+, etc. Three levels of thematic coding were performed using Dedoose and included input from community councils. Coding teams comprised of 3 coders compared for corroboration and recoding continued until coders reached agreement. Results: Five FGs and 12 KIIs (N=37) were conducted with persons aged 40 and above. Participants were CHamoru (46%), Filipino (59%), female (59%), and male (41%). In Guam CRC prevention preferences varied by age and gender; those in their 40s preferred culturally tailored video and less preference for an online module compared to groups age 50, and men identified the need for more awareness and outreach. Filipinos in Hawai‘i were not aware of CRC and prevention prioritizing economic obligations (job) over seeking health services. The preferred characteristics of culturally tailored CRC prevention education in Guam and Hawai‘i were trusted knowledge sources to deliver information, storytelling as a format, and involving families. Participants in Guam also preferred online sources while Hawai‘i preferred all types of media in Filipino languages. Conclusion. CHamoru and Filipinos in Guam and Hawai‘i are receptive to family as a source of information and support for CRC prevention, and hearing personal stories motivates CRC screening. Findings give insight toward age-and culturally-tailored CRC screening education with site specific preferences. Findings will be used to develop family-focused interventions for CHamoru and Filipinos to improve CRC screening. Citation Format: Tressa P. Diaz, Angela Sy, Jena Funakoshi, Elizabeth Elmore, Santino Camacho, Alisa Peralta, Marc Rollon. Colorectal cancer screening education intervention for Chamoru and Filipinos in Guam and Hawai‘i: Recommendations for culturally and age relevant education [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B045.

Bioengineered Anthocyanin-Enriched Tomatoes: A Novel Approach to Colorectal Cancer Prevention.

Colorectal cancer (CRC) remains a significant global health challenge, with barriers to effective prevention and treatment including tumor recurrence, chemoresistance, and limited overall survival rates. Anthocyanins, known for their strong anti-cancer properties, have shown promise in preventing and suppressing various cancers, including CRC. However, natural sources of anthocyanins often fail to provide sufficient quantities needed for therapeutic effects. Bioengineered crops, particularly anthocyanin-enriched tomatoes, offer a viable solution to enhance anthocyanin content. Given its large-scale production and consumption, tomatoes present an ideal target for bioengineering efforts aimed at increasing dietary anthocyanin intake. This review provides an overview of anthocyanins and their health benefits, elucidating the mechanisms by which anthocyanins modulate the transcription factors involved in CRC development. It also examines case studies demonstrating the successful bioengineering of tomatoes to boost anthocyanin levels. Furthermore, the review discusses the effects of anthocyanin extracts from bioengineered tomatoes on CRC prevention, highlighting their role in altering metabolic pathways and reducing tumor-related inflammation. Finally, this review addresses the challenges associated with bioengineering tomatoes and proposes future research directions to optimize anthocyanin enrichment in tomatoes.

Abstract A080: Improving outcomes: Addressing racial and ethnic disparities in colorectal cancer genomic research

Abstract Colorectal cancer (CRC) is the fourth most common cancer diagnosed in the United States (U.S.). This disease presents notable health disparities among racial and ethnic minorities in the U.S. Native Americans (NA) and non-Hispanic Blacks (NHB) exhibit the highest incidence and mortality rates for CRC compared to non-Hispanic Whites (NHW). These disparities are driven by a combination of factors, including socioeconomic inequalities, access to healthcare, lifestyle habits, and genetic susceptibilities. Minority populations often face delays in diagnosis and treatment, leading to advanced disease stages at presentation and poorer outcomes. Addressing these disparities through cancer genomics is essential for developing effective, personalized treatments that can improve outcomes for underrepresented populations. Comprehensive genomic studies can reveal genetic mutations and biomarkers unique to these groups, facilitating targeted therapies and preventive measures tailored to their specific needs. To address these disparities, we conducted an analysis of U.S. population-based colorectal cancer studies within 3 cancer genomic databases: the National Cancer Institute’s Genomic Data Commons, the AACR Project GENIE, and cBioPortal. We identified 13 studies suitable for inclusion, calculating incidence percentages across all racial and ethnic categories. Our analysis encompassed a total of 20,295 patients. Among the analyzed patients, the racial distribution was as follows: NHW (68.5%), Asians (5.30%), NHB (7.7%), Other (5.6%), NA (0.2%), Pacific Islander/Native Hawaiian (0.07%), and not reported (12.7%). Ethnic data was missing for 24.1% (n=4,895) of the patients. Samples were predominantly from individuals identified as Not Hispanic (68.4%), while Hispanic individuals constituted 7.5%. Our results show significant underrepresentation of NHB, NA and Hispanic patients in CRC genomic databases highlighting a disparity between expected and actual representation. These findings underscore the critical need for inclusive research practices. Addressing these disparities in cancer genomics is imperative to develop equitable, effective treatments and improve health outcomes for all populations. Ensuring diverse representation in genomic databases will enhance the understanding of genetic differences across populations, inform targeted therapies, and ultimately contribute to reducing CRC disparities. By addressing these disparities, we can move towards a future where all populations benefit equally from advancements in CRC treatment and prevention, thus improving survival rates and quality of life for minority groups. Citation Format: Gabriela Arroyo Figueroa, Tim F. Greten, Cecilia Monge. Improving outcomes: Addressing racial and ethnic disparities in colorectal cancer genomic research [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A080.

Abstract A150: Improving FIT and colonoscopy animated videos for colorectal cancer screening: An application of learner verification and revision

Abstract Latino adults in the U.S. have low rates of colorectal cancer (CRC) screening. Using at-home fecal immunochemical tests (FIT) can improve screening rates. This study builds upon three-minute instructional animated videos originally created by the Colorectal Cancer Prevention Network that our team previously translated into Spanish. In the current study, we employed a user-centered approach, known as learner verification and revision (LV&R), to elicit patients’ input on the videos. These videos will be used as part of a text-based intervention aimed at increasing FIT use among Latino adults aged 45-54. This study was part of a larger trial, Community Partnership for Telehealth Solutions to Counter Misinformation and Achieve Equity (PRIME), which aims to test an intervention that integrates the videos with social-needs navigation to boost CRC screening within Latino communities. LV&R integrates theories of health communication and qualitative research to tailor interventions to the needs of target populations. To solicit feedback on the two videos (one on FIT, one on colonoscopy), we interviewed 24 patients (46% male) from a large urban community clinic in Los Angeles. Patients were age-eligible for CRC screening, had been mailed a FIT, texted a link to the videos, and spoke English or Spanish (54% preferred Spanish). Interviews asked about acceptability, comprehension, actionability, and cultural relevance of the videos among our target audience. Interviews were recorded, transcribed, and summarized using rapid qualitative analysis techniques. Interviews revealed positive perceptions of both videos' accessibility, content, and appeal. Participants appreciated the videos’ straightforward language and clear instructions, which were found to be culturally and linguistically acceptable across English and Spanish-speakers. The videos were viewed as informative and persuasive, motivating participants to consider or complete CRC screening and share videos with others. The videos aided in dispelling misinformation related to screening with FIT and/or colonoscopy, particularly for those who had never screened for CRC. Participants liked the length of the videos along with use of appropriate humor to convey complex steps in the screening process. Participants suggested minor improvements such as adding language related to bowel prep, screening guidelines, communication of results, and reassuring language to help with fears to enhance the videos' effectiveness. Overall, these findings underscore the importance of culturally responsive, informative, and engaging materials in promoting CRC screening awareness and participation. Latino patients reported high acceptability, persuasiveness, helpfulness, and cultural appropriateness of animated videos sent via text to educate patients about FIT and colonoscopy. Suggestions for improvement centered on providing more facts about CRC, emphasizing that both men and women are at risk, adding reassuring language to encourage individuals to overcome any fears, and providing more resources for further information. Citation Format: Jennifer S. Rivelli, Jennifer L. Schneider, Blake W. Locher, Katherine A. Vaughn, Meagan C. Shaw, Gloria D. Coronado, Esmeralda Ruiz, Jamie H. Thompson, Anne Escaron. Improving FIT and colonoscopy animated videos for colorectal cancer screening: An application of learner verification and revision [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A150.

Abstract A129: So much of everything is rooted and caring for the family:” Community-Informed Colorectal Cancer Screening Education Recommendations for Filipinos in Hawaiʻi

Abstract Background. Colorectal cancer (CRC) incidence in Hawai‘i is higher than the U.S. with the highest age-adjusted rates among Filipinos. Among Asian and Pacific Islander ethnic subgroups in Hawaiʻi, Filipinos have the lowest CRC screening rates (69.9) compared to Japanese (82.0), and Native Hawaiians (73.3). Majority of CRC diagnoses can be prevented by CRC screening. This qualitative pilot study examined descriptive cognitive and cultural beliefs associated with CRC and screening and recommendations for culturally relevant prevention to reach Filipinos in Hawaiʻi. Methods. Key informant interviews were conducted in English with Ilokano translation when needed. Questions covered participants' knowledge about CRC and screening and their preferences in receiving CRC prevention education. Interviews lasted 15-30 minutes and were transcribed verbatim. Using Dedoose, two coders used inductive thematic coding. Codes were compared for corroboration, a referee was included when needed, and recoding continued until coders reached agreement. Results. Eleven females and three males (N=12) aged 50+ who identified as Filipino were interviewed. A total of 293 codes were created under 12 primary themes, e.g., “CRC attitudes and beliefs,” “family,” “culture-deterrents.” Common themes across interviewees were : 1) Health is not a priority 2) Family as motivation 3) No/limited knowledge of colorectal cancer 4) Education preferred through personal experiences and familiar relationships. Knowledge of CRC was low (N=9/12). Healthcare is often deprioritized due to cultural beliefs (N=11/12), busy schedules (N=8/12), fear of diagnosis (N=8/12), and, with economic pressures leading participants to prioritize work over health (N=8/12). However, strong familial motivations drive participants to take preventive health measures to avoid burdening their loved ones (N=7/12). Culturally tailored CRC prevention education programs should incorporate language and cultural relatability (n=10/12), storytelling (N=9/12),, and trusted medical authority (N=8/12).Conclusion. Addressing the identified barriers (limited knowledge) and leveraging strong family values will foster participation in CRC screening and participation in programs promoting screening. Personable and culturally tailored education that fosters emotional and relatable connections encourages participants' motivation and understanding of CRC to effectively reach Filipino communities in Hawaiʻi. Findings provide insight toward developing novel, culturally tailored interventions for Filipino families to increase CRC screening participation in this Asian community who experience screening disparities. Citation Format: Jena Funakoshi, Alisa Peralta, Marc Rollon, Tressa P. Diaz, Angela Sy. So much of everything is rooted and caring for the family:” Community-Informed Colorectal Cancer Screening Education Recommendations for Filipinos in Hawaiʻi [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A129.

Diurnal timing of physical activity and risk of colorectal cancer in the UK Biobank

BackgroundPhysical activity reduces colorectal cancer risk, yet the diurnal timing of physical activity in colorectal cancer etiology remains unclear.MethodsThis study used 24-h accelerometry time series from UK Biobank participants aged 42 to 79 years to derive circadian physical activity patterns using functional principal component analysis. Multivariable Cox proportional hazard models were used to examine associations with colorectal cancer risk.ResultsAmong 86,252 participants (56% women), 529 colorectal cancer cases occurred during a median 5.3-year follow-up. We identified four physical activity patterns that explained almost 100% of the data variability during the day. A pattern of continuous day-long activity was inversely associated with colorectal cancer risk (hazard ratio (HR) = 0.94, 95% confidence interval (CI) = 0.89–0.99). A second pattern of late-day activity was suggestively inversely related to risk (HR = 0.93, 95% CI = 0.85–1.02). A third pattern of early- plus late-day activity was associated with decreased risk (HR = 0.89, 95% CI = 0.80–0.99). A fourth pattern of mid-day plus night-time activity showed no relation (HR = 1.02, 95% CI = 0.88–1.19). Our results were consistent across various sensitivity analyses, including the restriction to never smokers, the exclusion of the first 2 years of follow-up, and the adjustment for shift work.ConclusionsA pattern of early- plus late-day activity is related to reduced colorectal cancer risk, beyond the benefits of overall activity. Further research is needed to confirm the role of activity timing in colorectal cancer prevention.

Correlation between gut microbiota dysbiosis and colorectal cancer: review

Introduction and Purpose: The human gut microbiota, comprising a diverse consortium of approximately 100 trillion microorganisms, is integral to maintaining health and modulating disease processes. Its development begins at birth, influenced by maternal microbiota and environmental factors. Dysbiosis, defined as an imbalance in the gut microbial composition, has been implicated in a range of gastrointestinal pathologies, including colorectal cancer (CRC). This review endeavors to elucidate the relationship between gut microbiota and CRC, examining the impact of specific bacterial taxa on the pathogenesis CRC. Description of the State of Knowledge: Gut microbiota encompasses a multitude of microbial species, with their composition differing along the gastrointestinal tract. Healthy gut microbiota perform essential functions such as pathogen protection, metabolic processes, and immune system modulation. Factors like diet and genetics significantly influence microbial composition. Dysbiosis contributes to CRC through inflammation, genotoxin production, and immune modulation. Specific bacteria, such as Fusobacterium nucleatum and Bacteroides fragilis, are associated with CRC. Mechanisms of carcinogenesis include bacterial adherence, invasion of epithelial cells, and activation of pro-inflammatory pathways. Summary:Understanding the gut microbiota's role in CRC highlights the importance of maintaining a balanced microbiome for cancer prevention. Dietary interventions promoting beneficial bacteria and reducing harmful species could mitigate CRC risk. Further research should prioritize the identification of microbial biomarkers for early CRC detection and the development of therapeutic strategies aimed at modulating the gut microbiota. These efforts will enhance CRC prevention and treatment modalities.

Niosomes containing enciprazine hydrochloride have been shown to efficiently inhibit the proliferation and induce apoptosis in colorectal cancer cells

Colorectal cancer (CRC), currently the second most widespread cancer globally, exhibits a higher incidence in young individuals. Advancements have been made in developing anti-colorectal cancer drugs, including cytotoxic chemicals, in the past few decades. There is a need for new and innovative medications to overcome the current challenges in cancer treatment. Recent research examined the efficacy of innovative formulations in the prevention of colorectal cancer. In this study, we evaluated the efficacy of a niosome formulation loaded with Enciprazine hydrochloride (Nio-USAN). We assessed the anti-colorectal cancer characteristics of Nio-USAN by employing several techniques including CCK-8, invasion test, MTT test, flow cytometry, and cell cycle assessment. Quantitative real-time PCR was utilized to assess the transcription of genes linked to apoptosis. The F1-Nio-USAN and F2-Nio-USAN have average sizes of 200 and 500 nm, respectively. The entrapment effectiveness (EE%) of the F1-Nio-USAN and F2-Nio-USAN was measured to be 85.32 ± 0.27 % and 87.12 ± 0.35 %, respectively. The F1-Nio-USAN group exhibited the following percentages of HT-29 cell states: 43 % early apoptosis, 21 % late apoptosis, 7 % necrotic, and 29 % viable. The levels of transcription for cas8, Bid, BAX, cas9, and cas3 were significantly elevated in the treatment groups as compared to the PBS control group (P < 0.001). In addition, the treatment group exhibited significantly reduced levels of BCL2 gene transcription compared to the PBS control group (P < 0.01). These results suggest that it may be possible to improve the efficacy of USAN formulations in combating cancer by utilizing noisome encapsulation.

Exploring the interplay of natural products and long non-coding RNAs in colorectal cancer: pathogenesis, diagnosis, and overcoming drug resistance.

Colorectal cancer (CRC) is recognized as one of the most prevalent malignancies, both in terms of incidence and mortality rates. Current research into CRC has shed light on the molecular mechanisms driving its development. Several factors, including lifestyle, environmental influences, genetics, and diet, play significant roles in its pathogenesis. Natural compounds such as curcumin, tanshinone, lycorine, sinomenine, kaempferol, verbascoside, quercetin, berberine, and fisetin have shown great promise in the prevention and treatment of CRC. Research has also highlighted the significance of non-coding RNAs (ncRNAs) as biomarkers and therapeutic targets in CRC. Among these, long non-coding RNAs (lncRNAs) have been found to regulate the transcription of genes involved in cancer. LncRNAs contribute to cancer stem cell (CSC) proliferation, angiogenesis, epithelial-mesenchymal transition (EMT), and chemoresistance. Specific lncRNAs, including GAS5, LNC00337, HOTAIR, TPT1-AS1, cCSC1, BCAR4, TUG1, and Solh2, play crucial roles in these processes. They hold potential as novel biomarkers, detectable in bodily fluids and tissues, and could serve as therapeutic targets due to their involvement in drug resistance and sensitivity. These insights could improve CRC treatment strategies, addressing resistance to chemotherapy and radiotherapy. This review article aims to provide a comprehensive analysis of the current knowledge regarding the effectiveness of natural anti-cancer agents in CRC treatment. Additionally, it offers an in-depth evaluation of lncRNAs in CRC, their role in the disease's progression, and their potential applications in its management.

Genetically predicted dietary intake and risks of colorectal cancer: a Mendelian randomisation study

BackgroundEffects of confounders on associations between diet and colorectal cancer (CRC) in observational studies can be minimized in Mendelian randomization (MR) approach. This study aimed to investigate observational and genetically predicted associations between dietary intake and CRC using one-sample MR.MethodsUsing genetic data of over 93 million variants, we performed a genome-wide association study to find genomic risk loci associated with dietary intake in participants from the UK Biobank. Then we calculated genetic risk scores of diet-related variants and used them as instrumental variables in the two-stage least square MR framework to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for associations. We also performed observational analyses using age as a time-scale in Cox proportional hazard models.ResultsAllele scores were calculated from 399 genetic variants associated with the consumption of of red meat, processed meat, poultry, fish, milk, cheese, fruits, vegetables, coffee, tea, and alcohol in participants from the UK Biobank. In MR analysis, genetically predicted fruit intake was significantly associated with a 21% decreased risk of CRC (HR = 0.79, 95% CI = 0.66–0.95), and there was a marginally inverse association between vegetable intake and CRC (HR = 0.85, 95% CI = 0.71–1.02). However, null findings were observed in multivariable analysis, with HRs (95% CIs) of 0.99 (0.98–1.01) and 0.99 (0.98–1.00) per increment of daily servings of fruits and vegetables, respectively.ConclusionDietary habits were attributable to genetic variations, which can be used as instrumental variables in the MR framework. Our study supported a causal relationship between fruit intake and a decreased risk of CRC and suggested an effective strategy of consuming fruits in the primary prevention of CRC.

Protein nutritional support: The prevention and regulation of colorectal cancer and its mechanism research

AbstractColorectal cancer (CRC) is a common malignant tumor of the digestive tract in China; its incidence rates and mortality rates have been on the rise in recent years, ranking third in terms of incidence and second in mortality. Rational dietary intervention plays an important role in human health, and prevention and adjuvant treatment of CRC through dietary supplementation is the most ideal and safest way to treat the disease at present. More importantly, dietary protein is the basis of our diet and the key nutrient to maintain the normal function of the human body. Therefore, this narrative review delivered an overview of the common causes and therapeutic treatments for CRC. It emphasized the importance of dietary interventions, with a particular focus on elucidating the distinct regulatory impacts of plant proteins, animal proteins, and their mixed proteins.

A Systematic Review of the Impact of Dietary and Lifestyle Factors on Colorectal Cancer Prevention in Gulf Cooperation Council Countries.

Colorectal cancer (CRC) remains a significant health burden in the Gulf Cooperation Council (GCC) countries, necessitating a deeper understanding of modifiable risk factors. Thus, the aim of the study was to evaluate the impact of dietary and lifestyle factors on the prevention of CRCin GCC countries. Studies were identified through electronic searches and reviewed based on relevant keywords. Databases searched included Ovid's MEDLINE, EMBASE, Google Scholar, and Web of Science, covering titles and abstracts published between January 1, 2000and July 25, 2024. The search strategy encompassed four thematic areas: "colorectal cancer,""adults above 18," "risk factors," and "GCC countries." The primary focus was on dietary and lifestyle factors. Two reviewers screened titles and abstracts to determine whether the inclusion criteria were met. A total of 1,883 records were identified across these databases. After removing 513 duplicate records, 1,370 records were screened based on titles and abstracts. Of these, 1,284 records were excluded, leaving 86 full-text articles for assessment. Eight studies were ultimately included in the final systematic review, consisting of seven case-control studies and one cross-sectional study. In GCC countries, a diet rich in fruits, vegetables, and fiber has shown protective effects against CRC, while high red meat and refined carbohydrate intake may increase risk. Regular physical activity reduces CRC risk, though the impact of smoking remains inconclusive. Evidence regarding dairy products is contradictory. There is a shortage of high-quality longitudinal studies, highlighting gaps in current research and underscoring the need for larger studies with consistent methodologies.

The interplay between diet and the enteric nervous system in the pathophysiology of colorectal cancer.

Colorectal cancer (CRC) represents the third most diagnosed cancer worldwide, with 1.9 million new cases reported annually. Notwithstanding the progress made in the field of therapeutic modalities and the advent of early diagnosis, CRC continues to represent the second most common cause of cancer-related mortality. The interactions between cancer cells and enteric nervous system (ENS) neurons are of great importance for the prevention and/or progression of CRC. Dietary factors play an important role in regulating both processes. The consumption of foods rich in polyphenols, omega-3 fatty acids, and the use of probiotics has been shown to promote proper ENS function, which in turn has been demonstrated to indirectly inhibit the development or progression of CRC. Conversely, a diet comprising a high proportion of saturated fats and refined sugars can induce oxidative stress and inflammation, which exacerbates the disease. Nutritional education and dietary modifications can reduce the incidence of new cases of CRC and improve prognosis. Further research into the potential anti- or pro-cancer effects of food substances is recommended.

Curcumin suppresses colorectal tumorigenesis through restoring the gut microbiota and metabolites

BackgroundCurcumin has been reported to have activity for prevention and therapy of CRC, yet its underlying mechanisms remain largely unknown. Recently, emerging evidence suggests that the gut microbiota and its metabolites contribute to the causation and progression of Colorectal cancer (CRC). In this study, we aimed to investigate if curcumin affects the tumorigenesis of CRC by modulating gut microbiota and its metabolites.MethodsForty male C57BL/6JGpt mice were randomly divided into four groups: negative control (NC), curcumin control, CRC model, and curcumin treatment (CRC-Cur) groups. CRC mouse model was induced by using azoxymethane (AOM) and dextran sodium sulfate (DSS), and the mice in CRC model and curcumin treatment groups received oral PBS or curcumin (150 mg/kg/day), respectively. Additionally, fecal samples were collected. 16 S rRNA sequencing and Liquid Chromatography Mass Spectrometry (LC-MS)-based untargeted metabolomics were used to observe the changes of intestinal flora and intestinal metabolites.ResultsCurcumin treatment restored colon length and structural morphology, and significantly inhibited tumor formation in AOM/DSS-induced CRC model mice. The 16S rRNA sequencing analysis indicated that the diversity and richness of core and total species of intestinal microflora in the CRC group were significantly lower than those in the NC group, which were substantially restored in the curcumin treatment group. Curcumin reduced harmful bacteria, including Ileibacterium, Monoglobus and Desulfovibrio, which were elevated in CRC model mice. Moreover, curcumin increased the abundance of Clostridia_UCG-014, Bifidobacterium and Lactobacillus, which were decreased in CRC model mice. In addition, 13 different metabolites were identified. Compared to the NC group, ethosuximide, xanthosine, and 17-beta-estradiol 3-sulfate-17-(beta-D-glucuronide) were elevated in the CRC model group, whereas curcumin treatment significantly reduced their levels. Conversely, glutamylleucine, gamma-Glutamylleucine, liquiritin, ubenimex, 5’-deoxy-5’-fluorouridine, 7,8-Dihydropteroic acid, neobyakangelicol, libenzapril, xenognosin A, and 7,4’-dihydroxy-8-methylflavan were decreased in the CRC group but notably upregulated by curcumin. Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis revealed enrichment in seven pathways, including folate biosynthesis (P < 0.05).ConclusionsThe gut microecological balance was disrupted in AOM/DSS-induced CRC mice, accompanied by metabolite dysbiosis. Curcumin restored the equilibrium of the microbiota and regulated metabolites, highly indicating that curcumin may alleviate the development of AOM/DSS induced colorectal cancer in mice by regulating intestinal flora homeostasis and intestinal metabolites.

Metagenomic analysis of colonic tissue and stool microbiome in patients with colorectal cancer in a South Asian population

BackgroundThe gut microbiome is thought to play an important role in the development of colorectal cancer (CRC). However, as the gut microbiome varies widely based on diet, we sought to investigate the gut microbiome changes in patients with CRC in a South Asian population.MethodsThe gut microbiome was assessed by 16s metagenomic sequencing targeting the V4 hypervariable region of the bacterial 16S rRNA in stool samples (n = 112) and colonic tissue (n = 36) in 112 individuals. The cohort comprised of individuals with CRC (n = 24), premalignant lesions (n = 10), healthy individuals (n = 50) and in those with diabetes (n = 28).ResultsOverall, the relative abundances of genus Fusobacterium (p < 0.001), Acinetobacter (p < 0.001), Escherichia-Shigella (p < 0.05) were significantly higher in gut tissue, while Romboutsia (p < 0.01) and Prevotella (p < 0.05) were significantly higher in stool samples. Bacteroides and Fusobacterium were the most abundant genera found in stool samples in patients with CRC. Patients with pre-malignant lesions had significantly high abundances of Christensenellaceae, Enterobacteriaceae, Mollicutes and Ruminococcaceae (p < 0.001) compared to patients with CRC, and healthy individuals. Romboutsia was significantly more abundant (p < 0.01) in stool samples in healthy individuals compared to those with CRC and diabetes.ConclusionDespite marked differences in the Sri Lankan diet compared to the typical Western diet, Bacteroides and Fusobacterium species were the most abundant in those with CRC, with Prevotella species, being most abundant in many individuals. We believe these results pave the way for possible dietary interventions for prevention of CRC in the South Asian population.

E3 ubiquitin ligase BTBD3 inhibits tumorigenesis of colorectal cancer by regulating the TYRO3/Wnt/β-catenin signaling axis

Clinical trials and studies have implicated that E3 ubiquitin ligase BTBD3 (BTB Domain Containing 3) is a cancer-associated gene. However, the role and underlying mechanism of BTBD3 in colorectal cancer (CRC) is not fully understood yet. Herein, our study demonstrated that the mRNA and protein levels of BTBD3 were decreased in CRC tissues and associated with TYPO3 and Wnt/β-catenin pathway. Our results showed that circRAE1 knockdown and TYRO3 overexpression activated Wnt/β-catenin signaling pathway and the EMT process-associated markers, indicating that circRAE1/miR-388-3p/TYRO3 axis exacerbated tumorigenesis of CRC by activating Wnt/β-catenin signaling pathway. In addition, overexpression of BTBD3 reduced CRC cell migration and invasion in vitro and inhibited tumor growth in vivo. Our data demonstrated that BTBD3 suppressed CRC progression through negative regulation of the circRAE1/miR-388-3p/TYRO3 axis and the Wnt/β-catenin pathway. Our data further confirmed that BTBD3 bound and ubiquitinated β-catenin and led to β-catenin degradation, therefore blocked the Wnt/β-catenin pathway and suppressed the CRC tumorigenesis. This study explored the mechanism of BTBD3 involved in CRC tumorigenesis and provided a new theoretical basis for the prevention and treatment of CRC.

Plasma Concentrations of Multiple Oxysterols and Risk of Colorectal Adenomas.

Oxysterols are metabolites of cholesterol that regulate the homeostasis of cholesterol, fatty acids, and glucose. These metabolites are generated throughout the body, either enzymatically or from oxidative stress, and are detectable in peripheral circulation. We previously reported that circulating 27-hydroxycholesterol (27-OHC), an endogenous selective estrogen receptor modulator, may be a risk factor for colorectal adenomas. Here, in addition to 27-OHC, we report on four other circulating oxysterols: 25-hydroxycholesterol, 24(S)-hydroxycholesterol, 7ɑ-hydroxycholesterol, and 4β-hydroxycholesterol. Oxysterol concentrations were measured using liquid chromatography/mass spectrometry from fasting plasma collected at baseline from 1,246 participants of the Vitamin D/Calcium Polyp Prevention Study, a multicenter adenoma chemoprevention trial. To evaluate multiple oxysterols simultaneously, we used both log-linear regression and Bayesian kernel machine regression models developed for analyses of complex mixtures adjusted for potential confounding factors. Higher circulating 7ɑ-hydroxycholesterol was associated with higher adenoma risk (Bayesian kernel machine regression-based multivariable-adjusted risk ratios (RR; for the 75th vs. 25th percentile, 1.22; 95% credible interval, CI, 1.04-1.42). In contrast, higher circulating 4β-hydroxycholesterol was associated with lower risk of these polyps (RR, 0.84; 95% CI, 0.71-0.99). The positive association with advanced adenoma risk that we previously reported for circulating 27-OHC persisted when controlling for other oxysterols (RR, 1.26; 95% CI, 0.98-1.62), including among those with advanced adenomas at baseline (RR, 1.75; 95% CI, 1.01-3.06). Prevention Relevance: Circulating concentrations of multiple oxysterols measured at the time of an initial colorectal adenoma diagnosis may be risk factors for subsequent incidence of these lesions. Novel colorectal cancer prevention strategies may target oxysterol formation.

Exploration and validation of ceRNA regulatory networks in colorectal cancer based on associations whole transcriptome sequencing

Colorectal cancer (CRC) is a wide-spread gastrointestinal cancer that is associated with augmented morbidity and mortality, and we do not yet have a deep understanding of its epidemiology and carcinogenicity. The transcriptome can reveal the complexity and heterogeneity of tumors and uncover new biomarkers or treatment options. In this study, we identified messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), round RNAs (circRNAs), and microRNAs (miRNAs) using whole-transcriptome sequencing and generated competing endogenous RNA (ceRNA) modulatory axes. We conducted whole transcriptome sequencing on 10 CRC and para-cancer (CRCP) samples and discovered 2465 differentially expressed (DE) mRNAs (DEmRNAs), 77 DE miRNAs (DEmiRNAs). 2852 DE lncRNAs (DElncRNAs) and 1477 DE circRNAs (DEcircRNAs). In addition, utilizing co-DE analysis, we generated the ceRNA axis. Subsequently, we employed the ceRNA axis to identify essential genes and corresponding associations with lncRNAs, circRNAs, and miRNAs in CRC. ceRNA regulatory network including mRNA-miRNA-lncRNA and mRNA-miRNA-circRNA. These modulatory axes potentially modulate the positive regulation of smooth muscle contraction, melanosome, plasma membrane, integral plasma membrane component and so on. Finally, the results of RNA sequencing (RNA-SEQ) were combined with the TCGA and GEO databases, and the DEGs strongly correlated with the TCGA-COAD overall survival (OS) as estimated by univariate cox and logarithmic rank analyses were cross-analyzed, and the co-upregulated DEGs were screened. Among the many DEs, KPNA2 was chosen for additional analysis. Using invitro experimentations, western blot, CCK8, EdU and other experiments were performed to verify the results. We found siRNA-based KPNA2 depletion reduces bladder cancer cells’ viability, migratory, and proliferative activities, which showed that the DEmRNA profiles were comparable to the sequencing information, confirming that the sequencing data were very reliable. These evidences highlight the ceRNA regulatory mechanisms in CRC and will aid future research into the molecular mechanisms behind colorectal cancer prevention and treatment.

Differential Outcomes in Colorectal Cancer Detection: A Comparative Study of Swedish Nationwide Screening and Fast-Track Diagnostic Pathways.

In 2021, a nation-wide screening program for colorectal cancer (CRC) was step-wise implemented in Region Örebro County (RÖC) for patients aged 60 to 74 years, utilizing the fecal immunochemical test (FIT) to refer patients for colonoscopy. Concurrently, the standardized care course for colorectal cancer (SCC-CRC), initiated in 2016, employs a fast-track pathway for patients with alarm symptoms to undergo colonoscopy. This study compares CRC screening colonoscopies with SCC-CRC colonoscopies in RÖC among patients aged 60 to 67 years. An initial analysis of the Swedish colorectal screening cohort was combined with a retrospective cohort study, analyzing data from 307 CRC screening patients and 441 age-matched SCC-CRC patients in RÖC. Data included demographics, colonoscopy participation rates, and pathology findings. Statistical analyses compared outcomes between the 2 groups. Among the screening group, 2% tested positive for FIT, with an 86% colonoscopy participation rate (N=9296). In RÖC, 266 screening patients underwent colonoscopy, with 10% diagnosed with CRC, compared with 20% in the SCC-CRC group. In addition, 39% of the screening group in RÖC were diagnosed with advanced adenomas, versus 15% in the SCC-CRC group. Screening participation was high, with effectiveness aligning with international counterparts. The SCC-CRC pathway excels in diagnosing CRC among symptomatic patients, while the nationwide screening program is effective in early detection of CRC and advanced adenomas. underscoring the importance of integrating and optimizing both approaches within the Swedish health care system to optimize CRC prevention and management.

HuR/miR-124-3p/VDR complex bridges lipid metabolism and tumor development in colorectal cancer.

Maintaining a balanced lipid status to prevent lipotoxicity is of paramount importance in various tumors, including colorectal cancer (CRC). HuR, an RNA-binding protein family member, exhibits high expression in many cancers possibly because it regulates cell proliferation, migration, invasion, and lipid metabolism. However, the role of HuR in the regulation of abnormal lipid metabolism in CRC remains unknown. We found that HuR promotes vitamin D receptor (VDR) expression to ensure lipid homeostasis by increasing Triglyceride (TG) and Total Cholesterol (TC) levels in CRC, thus confirming the direct binding of an overexpressed HuR to the CDS and 3'-UTR of Vdr, enhancing its expression. Concurrently, HuR can indirectly affect VDR expression by inhibiting miR-124-3p. HuR can suppress the expression of miR-124-3p, which binds to the 3'-UTR of Vdr, thereby reducing VDR expression. Additionally, a xenograft model demonstrated that targeting HuR inhibits VDR expression, blocking TG and TC formation, and hence mitigating CRC growth. Our findings suggest a regulatory relationship among HuR, miR-124-3p, and VDR in CRC. We propose that the HuR/miR-124-3p/VDR complex governs lipid homeostasis by impacting TG and TC formation in CRC, offering a potential therapeutic target for CRC prevention and treatment.