Colorectal Cancer Cases Research Articles

Uranium and Radium in Groundwater and Incidence of Colorectal Cancer in Georgia Counties, USA: An Ecologic Study.

Colorectal cancer (CRC) is the third most commonly occurring cancer in the United States, with higher incidence rates among Black populations. Groundwater concentrations of natural radionuclides uranium and radium have seldom been investigated in relation to CRC despite their known carcinogenicity. We investigate spatial patterns of CRC by race, and in relation to groundwater concentrations of uranium and radium, testing the hypothesis that uranium and radium in groundwater might differentially contribute to incident CRC in Black and White populations in counties of Georgia, USA. Black populations showed a higher incidence of CRC than White populations; the median incident rate difference was 9.23 cases per 100,000 (95% CI: 2.14, 19.40). Spatial cluster analysis showed high incidence clusters of CRC in similar regions for Black and White populations. Linear regression indicated there are, on average, 1-2 additional cases of colorectal cancer in counties with higher levels of radium in their groundwater, irrespective of race. Uranium was not associated with CRC. This ecologic study suggests that radium in groundwater may be linked with increased incidence of CRC, although it did not explain higher CRC incidence rates in Black populations. Further studies are needed to verify this association given the inherent limitations in the ecologic study design and the crude exposure assessment.

Functional links between the microbiome and the molecular pathways of colorectal carcinogenesis.

Colorectal cancer (CRC) is a common cancer, with a concerning rise in early-onset CRC cases, signalling a shift in disease epidemiology. Whilst our understanding of the molecular underpinnings of CRC has expanded, the complexities underlying its initiation remain elusive, with emerging evidence implicating the microbiome in CRC pathogenesis. This review synthesizes current knowledge on the intricate interplay between the microbiome, tumour microenvironment (TME), and molecular pathways driving CRC carcinogenesis. Recent studies have reported how the microbiome may modulate the TME and tumour immune responses, consequently influencing cancer progression, and whilst specific bacteria have been linked with CRC, the underlying mechanisms remains poorly understood. By elucidating the functional links between microbial landscapes and carcinogenesis pathways, this review offers insights into how bacteria orchestrate diverse pathways of CRC development, shedding light on potential therapeutic targets and personalized intervention strategies.

Impact of Tumoral β2-Adrenergic Receptor Expression on Chemotherapeutic Response and Prognosis in Patients with Advanced Colorectal Cancer.

The β2-adrenergic receptor (β2-AR) is a therapeutic target for circulatory agonists and exhibits oncogenic activity in several cancers. However, its role in advanced colorectal cancer (CRC) treated using chemotherapy remains unclear. We investigated the potential of β2-AR as a novel chemosensitivity marker and therapeutic target in inoperable CRC. β2-AR expression was evaluated immunohistochemically in 80 advanced or recurrent CRC cases for which untreated resected specimens were available before systemic chemotherapy implementation. We assessed the relationship among β2-AR protein expression, clinicopathological factors, therapeutic response, and prognosis. Furthermore, we evaluated the significance of β2-AR as an in vitro and in vivo therapeutic target using CRC cell lines and a CRC xenograft model treated with the β-blocker, propranolol, and other anticancer agents. High tumoral β2-AR expression was associated with shorter progression-free survival and chemotherapeutic resistance in patients treated with oxaliplatin-based regimens and bevacizumab-based regimens. We found no synergistic effect between propranolol and oxaliplatin. However, combined administration of propranolol and bevacizumab induced significant tumor shrinkage in the CRC xenograft model. β2-AR is a possible biomarker for chemosensitivity and prognosis in advanced CRC. Repositioning existing β-blockers could be beneficial for treating CRC resistant to existing treatment regimens.

Molecular genetic analysis of colorectal carcinoma with an aggressive extraintestinal immunohistochemical phenotype

Colorectal cancer (CRC) is a leading global cause of illness and death. There is a need for identification of better prognostic markers beyond traditional clinical variables like grade and stage. Previous research revealed that abnormal expression of cytokeratin 7 (CK7) and loss of the intestinal-specific Special AT-rich sequence-binding protein 2 (SATB2) are linked to poor CRC prognosis. This study aimed to explore these markers’ prognostic significance alongside two extraintestinal mucins (MUC5AC, MUC6), claudin 18, and MUC4 in 285 CRC cases using immunohistochemistry on tissue microarrays (TMAs). CK7 expression and SATB2-loss were associated with MUC5AC, MUC6, and claudin 18 positivity. These findings suggest a distinct "non-intestinal" immunohistochemical profile in CRC, often right-sided, SATB2-low, with atypical expression of CK7 and non-colorectal mucins (MUC5AC, MUC6). Strong MUC4 expression negatively impacted cancer-specific survival (hazard ratio = 2.7, p = 0.044). Genetic analysis via next-generation sequencing (NGS) in CK7 + CRCs and those with high MUC4 expression revealed prevalent mutations in TP53, APC, BRAF, KRAS, PIK3CA, FBXW7, and SMAD4, consistent with known CRC mutation patterns. NGS also identified druggable variants in BRAF, PIK3CA, and KRAS. CK7 + tumors showed intriguingly common (31.6%) BRAF V600E mutations corelating with poor prognosis, compared to the frequency described in the literature and databases. Further research on larger cohorts with a non-colorectal immunophenotype and high MUC4 expression is needed.

Spatiotemporal trends in the burden of colorectal cancer incidence and risk factors at country level from 1990 to 2019.

Worldwide, the incidence of colorectal cancer (CRC) continues to rise and remains a major public health concern. This study aimed to analyze the temporal and spatial trends in CRC incidence and related risk factors at the country level. Data on CRC and related risk factors were obtained from the Global Burden of Disease Study (GBD) 2019 study. Temporal trends were evaluated using estimated annual percentage change while spatial trends were analyzed using spatial autocorrelation and autoregression. Additionally, linear mixed-effects models were employed to identify risk factors linked to CRC incidence. Globally, from 1990 to 2019, the incidence cases of CRC increased by 157.23%. At the national level, the incidence of CRC increased in most countries, with the highest increases of age-standardized incidence rate (ASIR) in Equatorial Guinea, Vietnam, and China. In both 1990 and 2019, global spatial clustering of CRC ASIR highlighted hotspots in Europe, characterized by elevated CRC ASIR levels. A comparative analysis of risk factors between hotspot countries and others indicated that gender and alcohol use exerted greater influence in hotspots than elsewhere. Although from 1990 to 2019, the highest growth in ASIR of CRC has been observed in African, Asian, and Latin American countries, the hotspots are still concentrated in Europe. In the identified hotspots, gender and alcohol use exert a more significant impact on CRC incidence compared with other countries. Thus, we should pay attention to countries where the CRC incidence is increasing and these risk factors.

AI4CRC: A Deep Learning Approach Towards Preventing Colorectal Cancer

Each year, more than 1.9 million cases of colorectal cancer (CRC) are diagnosed worldwide. By 2040, the burden of colorectal cancer is estimated to reach 3.2 million new cases per year and 1.6 million deaths per year worldwide. As of 2024, it ranks as the third most prevalent form of cancer, contributing to over 10% of all new cancer cases annually, with a 5-year survival rate of only 65%. With effective early detection mechanisms in place, the survival rate could potentially increase to 90%. However, current detection mechanisms are manual and error-prone. This study presents a deep learning-based approach to automating the detection of polyps, the tumor that causes colorectal cancer, in the human colon. Various state-of-the-art deep learning models – including VGG, ResNet, DenseNet, and EfficientNet were trained and tested on a publicly available dataset. The findings of this study show that deep learning models can significantly automate the early diagnosis process of colorectal cancer with high accuracy, especially the DenseNet and EfficientNet models – attaining 99% and 99.4% respectively for both accuracy and F1 score metrics on the test dataset. This study validates the potential of deep learning to enhance the accuracy and reliability of colorectal cancer detection and prevention, ultimately contributing to better quality of diagnosis and patient outcomes.

Visceral Fat Thickness, Serum Adiponectin, and Metabolic Syndrome in Patients with Colorectal Adenomas.

Most cases of colorectal cancer (CRC) arise from adenomatous polyps. Identifying risk factors for colorectal adenoma (CRA) is critical for CRC prevention. Emerging evidence suggests a link between metabolic syndrome (MetS) and an elevated risk of CRA and CRC, potentially mediated by visceral obesity and adiponectin (APN). We aimed to evaluate the association between different markers of visceral obesity, serum APN, MetS, and the presence of CRA. A cross-sectional study was conducted at the University Clinical Center of Vojvodina, involving 120 patients, aged 40-75 years, who underwent colonoscopy between January 2022 and January 2023. Sixty patients with CRA were compared to 60 controls with normal colonoscopy findings. Visceral fat thickness (VFT) was measured using ultrasound (US), and bioelectrical impedance analysis (BIA) was used to assess visceral fat area (VFA). Serum APN levels, anthropometric measures, and MetS components were also evaluated. Patients with CRA had significantly higher VFT measured by US (p < 0.05), but no significant differences were found in VFA measured by BIA, waist circumference (WC), or waist-to-hip ratio (WHR). MetS was significantly more prevalent in the CRA group (55% vs. 31.6%, p < 0.05), and logistic regression confirmed MetS as a significant predictor of CRA presence (OR = 2.6). Serum APN levels were inversely correlated with visceral fat measurements and MetS (p < 0.01), but no significant difference in APN levels was observed between patients with and without CRA. This study highlights the importance of VFT measured by US and the presence of MetS as significant factors associated with CRA.

Choice of surgical treatment approach in patients with metastatic colorectal cancer complicated by intestinal obstruction

BACKGROUND: Every year more than 1 million new cases of colorectal cancer are diagnosed worldwide, with approximately 30% patients already having distant metastases. Colorectal cancer is often complicated, which makes chemotherapy challenging or, in some cases, impossible, therefore worsening the prognosis. As the first step, such patients need to undergo surgical treatment, in order to eliminate existing complications. However, what volume of surgery remains a discussion point among ongologists: a colostomy or a cytoreductive r2 resection to remove the primary tumor. AIM: To analyze the results of complex treatment in patients with metastatic colorectal cancer and to optimize surgical treatment approaches. MATERIALS AND METHODS: We conducted a study in Samara regional clinical Oncology dispensary (Samara, Russia), which included patients with metastatic colorectal cancer complicated by intestinal obstruction. Before treatment, all patients were examined according with current clinical standards. Subsequently, the patients were divided into two groups: the first group included patients who underwent cytoreductive surgery (r2 resection to remove the primary lesion due to the presence of colonic obstruction), and the second group included patients who underwent palliative surgery (colostomy or a bypass anastomosis in order to eliminate intestinal obstruction without removing the primary tumor). RESULTS: We found that postoperative complications in patients who had undergone primary tumor removal were significantly more prevalent. At the same time, however, the number of complications at the stage of chemotherapy, combined with angiogenesis inhibitor therapy, was significantly greater than in the group of patients in whom primary lesion was not removed. Complications that arose during chemotherapy affected the number of chemotherapy cycles performed. Discontinuation of chemotherapy affected event-free and overall survival. CONCLUSION: Timely identification and elimination of existing complications by removing the primary tumor focus before chemotherapy is an important component of an individual approach in order to develop treatment optimal tactics for patients with metastatic colorectal cancer.

Abstract C110: The role of the S100 family signaling pathway proteins in Hispanic colorectal cancer disparities

Abstract Colorectal cancer (CRC) is a global health concern, ranking as the second deadliest and third most diagnosed cancer. In the United States alone, it is estimated that there will be 152,810 new cases of CRC in 2024. CRC has an overall survival rate of 90% when detected in its early stages (Stage I/II). However, due to low screening rates, only 39% of CRC patients in the U.S. are diagnosed during the early stage, particularly among the minority groups like Hispanics. This disparity can be attributed to various factors, including limited access to health care facilities and socio-economic barriers. Among Hispanics, CRC diagnosis and screening rate are lower, resulting in a higher incidence of late-stage (Stage III/IV) diagnosis compared to Non-Hispanic Whites (NHW). Only 33% of Hispanics receive timely diagnosis, and merely 49% undergo recommended screening protocols, in comparison to a diagnosis rate of 35% and screening rate of 58% in NHW. Addressing this health disparity emphasizes the urgent need for targeted interventions to improve early screening and diagnosis within the Hispanic population. We hypothesize that genetic factors across different ethnicities/races may influence gene expression patterns during various stages, thereby contributing to CRC tumorigenesis and progression. To enhance the chances of identifying markers for early detection and diagnosis among Hispanics, we aim to identify new ethnicity-specific transcriptomic profiles. RNA sequencing of Hispanic CRC, NHW CRC and their respective normal tissues adjacent to the tumor (NAT), revealed unique sets of differentially expressed genes (DEGs) with a log2 foldchange of ≥ 2.0 and ≤ -2.0 and p-adjusted value ≤ 0.05 in Hispanic (1831) and NHW (1225) CRC populations compared to their respective NATs. Further analysis identified DEGs specific to early (1012) and late (765) stages of CRC within the Hispanic population, as compared to the respective stages in the NHW. Ingenuity Pathway Analysis (IPA) was used to uncover significant DEGs associated with the S100 family signaling pathway in Hispanic CRC samples. Previous studies have indicated the involvement of the S100 family proteins and their signaling pathways in CRC development, progression, metastasis, and drug resistance through interactions with WNT/β-catenin, RAGE, MAPK and NF-κβ signaling pathways. Our investigation of DEGs within the S100 signaling pathway and their interaction with downstream effectors suggests differential expression of genes crucial in cellular processes, including matrix metallopeptidases (MMP), mitogen-activated protein kinases (MAP2K) and Wingless-related integration site (WNT) family proteins. Exploring these proteins and their downstream effectors in Hispanic CRC tissues and organoids would elucidate specific functional attributes influencing CRC progression. Understanding the interaction of proteins identified in this study may serve as potential ethnicity-specific biomarkers or targets for the development of novel therapeutic interventions for early-stage CRC diagnosis in Hispanics. Citation Format: Soumya Nair, Brian I Grajeda, Sourav Roy. The role of the S100 family signaling pathway proteins in Hispanic colorectal cancer disparities [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 C110.

Abstract C103: Exploring ethnicity-specific molecular mechanism of cholesterol and fatty acid synthesis pathway in Hispanic colorectal cancer

Abstract Colorectal cancer (CRC) is the most prevalent gastrointestinal cancer, the third most common malignancy and the second leading cause of cancer-related mortality worldwide. The American Cancer Society (ACS) estimates 152,810 new cases of colorectal cancer, with an estimated 53,010 deaths in 2024. Typically diagnosed in older adults, CRC incidence is rising among younger individuals, particularly in Hispanics (16.5%) compared to non-Hispanic whites (8.7%). Due to the lack of timely screenings in this ethnic group, further research is crucial to identify novel biomarkers and therapeutic targets for improved early detection and intervention. To accomplish this goal, we performed RNA-sequencing of Hispanic and non-Hispanic White (NHW) CRC tissues. The transcriptomic analysis revealed differential gene expression patterns in Hispanic and NHW populations when compared to respective normal adjacent tissues (NATs). We identified 3577 differentially expressed genes (DEGs) in Hispanic CRC samples and 2971 DEGs in NHW CRC samples, of which 1831 DEGs were unique to Hispanic. Based on the preliminary analysis we hypothesized that unique DEGs from the Hispanic population could help identify potential pathways contributing to CRC progression. Among these 1831 unique DEGs, many of the genes are associated with cholesterol and fatty acid synthesis pathway. The cholesterol biosynthesis pathway is a highly diverse and interconnected signaling pathway, playing essential roles in cellular function and systemic homeostasis. Its complexity and regulatory mechanisms make it a critical area of study in cancer. Studies indicate that Hispanics and African Americans with high cholesterol tend to have higher Body mass index (BMI) levels compared to Whites which has an increased risk of colorectal cancer. However, the role of cholesterol metabolism and fatty acid metabolism in CRC have not been studied from the Hispanic health disparities perspective. From the 1831 DEGs, we selected those in the cholesterol and fatty acid synthesis pathways with significant log2 fold changes (≤ -2 or ≥ +2) and adjusted p-values (FDR ≤ 0.05). Our bioinformatics analysis identified four key DEGs: LCN2, DHCR7, PCSK9 and SQLE. The expression levels of these genes were examined in Hispanic CRC vs. NHW CRC tissue samples using qRT-PCR. Elevated expression of LCN2 and SQLE was observed in late-stage Hispanic CRC tissues compared to NHW CRC tissues, while DHCR7 exhibited high expression in early-stage Hispanic CRC. On the other hand, PCSK9 showed low expression in both early and late stages of Hispanic CRC, suggesting potential ethnicity-specific molecular signatures in CRC progression. Moving forward, protein level studies and functional analysis of these DEGs in Hispanic CRC tissues and organoids will enhance our understanding of the role of cholesterol and fatty acid synthesis pathway proteins. Thus, elucidating novel molecular mechanisms underlying CRC progression could lead to identification of potential Hispanic specific biomarkers and therapeutic targets for early diagnosis and intervention. Citation Format: Somrita Roy, Soumya Nair, MD Zahirul Islam Khan, Sourav Roy. Exploring ethnicity-specific molecular mechanism of cholesterol and fatty acid synthesis pathway in Hispanic colorectal cancer [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 C103.

Abstract A038: Uncovering the role of social determinants of health in racial disparities in cancer incidence in Alabama

Abstract Purpose Black-White racial disparities have long been recognized in cancer incidence. National estimates may not reflect racial disparities in individual states. In Alabama (AL), a primarily rural underserved state, Black Americans are more often diagnosed with breast, prostate and colorectal cancer (CRC), with Black men more often diagnosed with lung cancer. Although rurality and area-level deprivation, as social determinants of health (SDoH), have been associated with cancer, their role in explaining racial disparities in cancer incidence remains unknown. We assessed racial disparities in breast, prostate, CRC and lung cancer incidence in AL. Methods We used the Alabama Statewide Cancer Registry (ASCR) to collect data on incident cases of breast, prostate, CRC and lung cancers diagnosed between January 1, 2010 and December 31, 2019. We categorized cases according to age group (0-14, 15-19, 20-24, 25-34, 35-44, 45-64, 65-84, ≥85 years), racial/ethnic group (non-Hispanic Black/White), rural-urban status (defined by AL Rural Health Association), and national area deprivation index (ADI) quartile (Q1-Q4) of census tract at diagnosis. For each combination of these variables, we calculated age-adjusted incidence per 100,000. We conducted bivariate descriptive analysis of incidence rates by race, and rural-urban status and ADI quartile stratified by race. Results Incidence of breast, prostate and CRC cancer was higher in Black versus White individuals (breast 143 vs 127; prostate 206 vs100; CRC males 57.2 vs 45.4, CRC females 42.7 vs 32.6). Lung cancer incidence was higher in Black males and White females (Black vs White: males 82.7 vs 77.6; females 36.9 vs 49.9). In all cancers, racial differences in incidence existed by rural versus urban status (breast Black 142 vs 144, breast White 131 vs 124; prostate Black 204 vs 207, prostate White 101 vs 99.4; male CRC Black 60 vs 55.3, male CRC White 47.7 vs 43, female CRC Black 43.5 vs 42.3, female CRC White 35.2 vs 30.2; male lung Black 84.5 vs 81.7, male lung White 85.1 vs 70.2, female lung Black 31.4 vs 40.1, female lung White 54.4 vs 45.6). In all cancers, racial differences in incidence also existed by ADI status (reporting Q1 vs Q4) [breast Black 190 vs 130, breast White 144 vs 118; prostate Black 269 vs 189, prostate White 109 vs 101; CRC male Black 64.2 vs 56.7, CRC male White 41.2 vs 49.7, CRC female Black 43.4 vs 43.5, CRC female White 29.5 vs 36.6; lung male Black 73.7 vs 91, lung male White 57.9 vs 97.6, lung female Black 41 vs 37.7, lung female White 40.8 vs 60.7]. Conclusions In AL, racial differences in incidence rates for each of the most common cancers exist overall and by key SDoH. Generally, Black individuals have higher rates of cancer, particularly those in rural and low ADI areas. Next, we will perform a decomposition analysis to decompose the Black/White differences in incidence into a portion explained and unexplained by rural-urban status and ADI. Ultimately, these results may inform interventions in a rural underserved state with a large Black population at higher risk of cancer. Citation Format: Mackenzie E. Fowler, Hayden Reeves, Melissa J. Smith, Geetanjali Saini, Mahak Bhargava, Ritu Aneja. Uncovering the role of social determinants of health in racial disparities in cancer incidence in Alabama [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 A038.

Abstract A048: Association between ambient particulate matter and colorectal cancer incidence: The Multiethnic Cohort Study

Abstract Background: Growing evidence suggests that air pollution may be a risk factor for colorectal cancer (CRC). We examined the association between ambient particulate matter (PM) exposure and CRC risk within the Multiethnic Cohort Study (MEC), representing the first study to include a large sample of racial and ethnic minoritized populations. Methods: The MEC is a prospective study that recruited, from 1993 through 1996, men and women ages 45-75 years largely from five racial and ethnic groups (African American, Japanese American, Latino, Native Hawaiian, and Non-Hispanic White) living in Hawai‘i and California. This study included 98,675 California MEC participants, residing predominately in Los Angeles County. Satellite-based PM2.5 (PM with an aerodynamic diameter &amp;lt;2.5μm) exposures were estimated from a published spatiotemporal model. Kriging interpolation was used to estimate PM10 (PM &amp;lt;10μm) exposures using routine air monitoring data from the US Environmental Protection Agency. Time-varying PM exposures were assessed from time of recruitment through 12/31/2018. Incident invasive CRC cases were identified via linkage with the California Cancer Registry (n=3,217). Cox proportional hazards models were used to examine the association between PM and CRC risk using age as the time metric, with strata defined by age at cohort entry and race and ethnicity, and adjusting for demographic and lifestyle factors. Heterogeneity of the PM-CRC association was assessed by sex, race and ethnicity, and CRC subsite (right colon, left colon, rectum). Results: Risk of CRC increased with PM2.5 (per 10μg/m3 hazard ratio [HR] 1.13, 95% confidence interval [CI] 0.96-1.33) with a larger HR observed among females (HR 1.29, 95% CI 1.03-1.62) than males (HR 0.96, 95% CI 0.76-1.22) (Pheterogeneity=0.24). CRC risk was positively associated with PM2.5 across race and ethnicity (except for African American participants) with the largest HR observed among Latino participants (HR 1.47, 95% CI 1.03-2.08) (Pheterogeneity=0.20). There was no statistically significant heterogeneity of PM2.5 effect by tumor subsite (Pheterogeneity=0.07); although larger HRs were seen for left colon (HR 1.52, 95% CI 1.08- 2.14) and rectal cancers (HR 1.54, 95% CI 1.05-2.25) than right colon cancers (HR 1.09, 95% CI 0.88-1.35). PM10 was not associated with CRC risk (per 10 μg/m3; HR 1.02, 95% CI 0.93-1.22) with no evidence of heterogeneity in associations by sex or race and ethnicity (respective Pheterogeneity 0.75, 0.44). Although HRs for PM10 appeared to differ by CRC subsite (Pheterogeneity=0.03), the 95% CI of these HRs included the null (right HR 0.95, 95% CI 0.84-1.06; left HR 1.13, 95% CI 0.95-1.35; rectal HR 1.18, 95% CI 0.97-1.43). Conclusions: Preliminary findings suggest that PM2.5 exposure is associated with CRC risk with larger associations in females and, possibly, for left colon and rectal cancer. Additional studies are needed to confirm these findings and evaluate the potential biological pathways underlying these associations. Citation Format: Ugonna Ihenacho, Chiuchen Tseng, Jun Wu, Scott Fruin, Timothy V. Larson, Salma Shariff-Marco, Loïc Le Marchand, Daniel O. Stram, Lynne R. Wilkens, Christopher A. Haiman, Beate Ritz, Iona Cheng, Anna H. Wu. Association between ambient particulate matter and colorectal cancer incidence: The Multiethnic Cohort Study [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 A048.

A Case of Colorectal Cancer Detected by Vascular Graft Infection Caused by &lt;i&gt;Listeria Monocytogenes&lt;/i&gt;

A Case of Colorectal Cancer Detected by Vascular Graft Infection Caused by &lt;i&gt;Listeria Monocytogenes&lt;/i&gt;

Repeat Faecal Immunochemical Testing for Colorectal Cancer Detection in Symptomatic and Screening Patients: A Systematic Review and Meta-Analysis.

Faecal immunochemical testing (FIT) is widely used in bowel screening programmes and assessing symptomatic patients for suspected colorectal cancer (CRC). The evidence for single test performance of FIT in both settings is considerable; however, the use of a repeat test to increase sensitivity remains uncertain. We aimed to review what increase in test positivity would be generated by additional FITs, whether a repeated FIT detects previously missed CRC and advanced colorectal neoplasia (ACRN), and to estimate the sensitivity of double-FIT strategies to diagnose CRC and ACRN. A systematic search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) was performed using key search terms. Studies reporting the use of more than one FIT in the same screening round or planned assessment of a single symptomatic patient episode were included. Studies were categorised by the reported study population into asymptomatic, mixed (cohorts of combined asymptomatic, symptomatic, or high-risk surveillance), or symptomatic cohorts. A total of 68 studies were included for analysis (39 asymptomatic, 21 mixed, 7 symptomatic, and 1 study with discrete asymptomatic and symptomatic data). At a threshold of 10 µg Hb/g, the two-test positivity ranged between 8.1 and 34.5%, with an increase from the second test of 3-9.2 percentage points. Four out of five studies comparing one versus two tests for diagnosing CRC at 10 µg Hb/g identified additional cases with the second test, with a minimum of 50% reduction in missed CRC. At a threshold of 20 µg Hb/g, the second test increased the positivity by 1.3-6.7 percentage points, with a two-test positivity of between 5.1 and 25.0%. Using a threshold of 20 µg Hb/g, five out of seven studies had a 25% reduction in missed CRC. A meta-analysis estimated the double-FIT sensitivity at 10 µg Hb/g for CRC in mixed-risk and symptomatic cohorts to be 94% and 98%, respectively. Repeated use of FIT helps to diagnose more cases of CRC with a moderate increase in positivity. A double-FIT strategy at 10 µg Hb/g in mixed and symptomatic cohorts has a very high sensitivity for CRC.

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.

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

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

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.

The prognostic significance of growth pattern, tumor budding, poorly differentiated clusters, desmoplastic reaction pattern and tumor-stroma ratio in colorectal cancer and an evaluation of their relationship with KRAS, NRAS, BRAF mutations

Growth pattern (GP), tumor budding (TB), poorly differentiated clusters (PDC), desmoplastic reaction pattern (DRP) and tumor-stroma ratio (TSR) are prognostic histomorphological parameters in colorectal cancer (CRC). Correlations between these parameters, their individual prognostic values, and their relationship with KRAS/NRAS/BRAF mutations have not been comprehensively examined. We aimed to investigate these associations, which have not been previously explored in this combination. 126 CRC cases were included. GP, TB, PDC, DRP and TSR were evaluated by two experienced pathologists. KRAS/NRAS/BRAF mutation profile were determined using qPCR. Demographic, clinicopathological and survival data were recorded. Interrelations were investigated by statistical analysis. Infiltrative GP was more frequent in high-score TB, PDC-G3, and stroma-high tumors (p < 0.05). High-score TB was more common in PDC-G3 and stroma-high tumors (p < 0.05). Immature DRP was more frequent in stroma-high tumors (p = 0.014). Among histomorphological parameters, a significant relationship was found only between infiltrative GP and the presence of KRAS mutation (p = 0.023). Moreover, GP was significantly associated with pT, lymphatic invasion, perineural invasion (p < 0.05). Effects on survival were assessed using Kaplan-Meier method and Cox proportional hazards model. TB and PDC were identified as independent predictors of overall survival. Higher TB score (p = 0.008) and higher PDC grade (p = 0.013) lead to worse survival. Interestingly, GP, DRP, TSR or KRAS/NRAS/BRAF mutations were not associated with overall survival. Our results highlight the prognostic significance of TB and PDC. We suggest incorporating TB and PDC into routine CRC reports. The association of KRAS mutation with infiltrative GP supports its role in the acquisition of invasive behavior.

Differences in characteristics and outcomes between early-onset colorectal cancer and late-onset colorectal cancers

IntroductionColorectal cancer (CRC) represents a significant health burden worldwide, with a notable increase in early-onset colorectal cancer (EOCRC) cases, defined as those diagnosed before the age of 50 years. Materials and methodsUsing data from Taiwan's national cancer registry and a retrospective cohort from Chang Gung Memorial Hospital, this study analyzed CRC cases diagnosed between 2008 and 2019. The analysis compared the EOCRC and late-onset CRC (LOCRC) groups in terms of clinicopathological characteristics, pre-diagnostic symptoms, and survival outcomes. ResultsThe analysis revealed a continuous increase in the annual incidence of EOCRC, with colon cancer and rectal cancer rising by 3.2 % and 3.3 %, respectively. Patients with EOCRC presented with more aggressive disease characteristics, such as signet-ring cell adenocarcinoma, mucinous adenocarcinoma, and poorly differentiated grade. Advanced stages at diagnosis, stages III and IV, were more common with EOCRC (62.4 %) than with LOCRC (50.3 %). Patients with EOCRC reported rectal bleeding, changes in bowel habits, and abdominal pain more frequently than those in the LOCRC group. There is a strong association between stool-related symptoms and left-sided CRC. Despite similar surgical outcomes, the 5-year cancer-specific survival rate of patients with stage IV EOCRC was significantly lower than that of patients with LOCRC (32.8 % vs. 51.9 %, p = 0.012). ConclusionThis study highlights a persistent rise in the incidence of EOCRC, with patients presenting with more aggressive disease and experiencing inferior survival. These findings underscore the importance of heightened awareness and early detection strategies for CRC, especially in younger populations, to improve the prognosis.

Assessing the Role of Flexible Sigmoidoscopy for Patients With Positive Fecal Immunochemical Test (FIT) and Rectal Bleeding as a Sole Symptom Within the Fast-Track Pathway.

Background Rectal bleeding is a frequent symptom, with causes ranging from benign conditions to serious diseases like colorectal cancer (CRC) and inflammatory bowel disease (IBD). In the UK, the two-week wait (2WW) referral pathway, which includes the fecal immunochemical test (FIT), plays a key role in triaging suspected CRC cases. This study evaluates the effectiveness of flexible sigmoidoscopy (FS) in detecting significant bowel pathologies (SBPs) in FIT-positive patients with isolated rectal bleeding. Methods We reviewed records of 344 patients with isolated rectal bleeding and a positive FIT result, referred to the 2WW pathway at York and Scarborough Teaching Hospitals NHS Foundation Trust from February to December 2023. All patients underwent colonoscopy. Findings from colonoscopy were used as a standard to compare with the expected reach of FS. Pathologies were categorized into SBPs (cancer, IBD, polyps ≥10 mm) and non-SBPs, and the location of SBPs in relation to the splenic flexure was also assessed. Results The average age of patients was 61.58 years. Significant bowel pathology (SBP) was identified in 89 of 344 (25.9%) patients, including 16 (18%) patients with cancer, 21 (23.6%) patients with IBD, and 52 (58.4%) patients with large polyps. All cases of cancer and IBD were found distal to the splenic flexure, while 21.1% (11/89) of large polyps were proximal. Higher FIT values (>100 µg Hb/g feces) and older age were significantly associated with SBPs. However, age and higher FIT values did not predict whether SBPs were proximal or distal. Conclusion For FIT-positive patients with isolated rectal bleeding, FS can serve as an effective initial diagnostic tool. Patients without detected cancer can be downgraded from the fast-track pathway to routine colonoscopy follow-up to avoid missing proximal premalignant lesions. This approach enhances resource utilization while ensuring comprehensive patient care. Further studies are needed to improve triage criteria and diagnostic accuracy within the 2WW pathway.