Colorectal Cancer Rates Research Articles

Integrated analysis reveals a novel 5-fluorouracil resistance-based prognostic signature with promising implications for predicting the efficacy of chemotherapy and immunotherapy in patients with colorectal cancer.

5-Fluorouracil (5-FU) has been used as a standard first-line treatment for colorectal cancer (CRC) patients. Although 5-FU-based chemotherapy and immune checkpoint blockade (ICB) have achieved success in treating CRC, drug resistance and low response rates remain substantial limitations. Thus, it is necessary to construct a 5-FU resistance-related signature (5-FRSig) to predict patient prognosis and identify ideal patients for chemotherapy and immunotherapy. Using bulk and single-cell RNA sequencing data, we established and validated a novel 5-FRSig model using stepwise regression and multiple CRC cohorts and evaluated its associations with the prognosis, clinical features, immune status, immunotherapy, neoadjuvant therapy, and drug sensitivity of CRC patients through various bioinformatics algorithms. Unsupervised consensus clustering was performed to categorize the 5-FU resistance-related molecular subtypes of CRC. The expression levels of 5-FRSig, immune checkpoints, and immunoregulators were determined using quantitative real-time polymerase chain reaction (RT‒qPCR). Potential small-molecule agents were identified via Connectivity Map (CMap) and molecular docking. The 5-FRSig and cluster were confirmed as independent prognostic factors in CRC, as patients in the low-risk group and Cluster 1 had a better prognosis. Notably, 5-FRSig was significantly associated with 5-FU sensitivity, chemotherapy response, immune cell infiltration, immunoreactivity phenotype, immunotherapy efficiency, and drug selection. We predicted 10 potential compounds that bind to the core targets of 5-FRSig with the highest affinity. We developed a valid 5-FRSig to predict the prognosis, chemotherapeutic response, and immune status of CRC patients, thus optimizing the therapeutic benefits of chemotherapy combined with immunotherapy, which can facilitate the development of personalized treatments and novel molecular targeted therapies for patients with CRC.

The epidemiology and demographic statistics of serrated adenocarcinoma.

e15645 Background: Serrated adenocarcinoma (SAC) is a recently-recognized variant of colorectal cancer (CRC) arising from precursor lesions of the serrated neoplastic pathway. Despite its novelty, SAC makes up around 10% of all CRCs and demonstrates worse patient prognosis than other forms. As rates of CRC, one of the most common cancers worldwide, continue to rise, further investigation must be done into new variants like SAC to improve its survivability and patient quality of life. This National Cancer Database (NCDB) analysis aims to evaluate the epidemiological factors and clinical characteristics of patients diagnosed with SAC. Methods: The 2004-2020 NCDB records were searched for patients with histologic diagnosis of SAC (N = 171) with the ICD-O-3 code 8213. This study utilized descriptive statistics to analyze demographics factors including age, sex, race, Hispanic status, educational attainment, insurance status, facility type, and Charlson-Deyo score. Results: From 2005-2020, 171 patients with an average age at diagnosis of 70.5 ± 11.3 years were diagnosed with serrated adenocarcinoma, with most (88%) cases demonstrating invasive behavior in the ascending colon (37%) or cecum (21%). The size of the tumors ranged from 1 - 200 mm, with an average size of 30.0 mm. The overwhelming majority of patients were white (93%) women (60%) living on average no more than 20 miles away from a hospital in metropolitan areas with populations over a million (49%). More patients were insured through Medicare (66%), receiving treatment at comprehensive community cancer (37%) or academic research programs (30%). Nearly all patients (95%) underwent surgery at the primary site, with a ninety-day survival rate of 88%. Among these, the most common procedure was subtotal colectomy or hemicolectomy (43%) followed by partial colectomy with segmental resection (22%), with 84% of patients showing no residual tumor after surgery. Alternate treatments included were chemotherapy (19%) and radiation therapy (8%). After five years, 68% of patients were alive, with the number falling to 35% after ten years. Conclusions: This study is the first on SAC to analyze NCDB data, presenting a larger sample than prior literature. With the commonality of colorectal cancer, the lack of research on SAC represents a significant knowledge gap. Interestingly, the data suggests that SAC predominantly develops in the ascending colon and cecum, conflicting with prior literature which suggested its tumors were more evenly distributed. Demographically, its diagnosed patients are mostly elderly, non-Hispanic whites insured by Medicare living in dense metropolitan areas near hospitals. These findings implicate that rural, aging communities could be impacted more severely by SAC, as they lack the healthcare infrastructure to obtain a proper diagnosis. To better define the link between demographic factors and effective diagnosis and treatment, further research is needed.

Enrollment strategies to promote inclusion in a colorectal cancer screening study.

e13530 Background: Colorectal cancer (CRC) is the second deadliest cancer in the U.S. and while rates vary among racial/ethnic groups, the Black community is disproportionately impacted with the highest incidence and mortality rates. Notably, CRC rates have also been rising among younger individuals aged 45 to 49. Recruitment of diverse and underrepresented groups, such as the populations described above, is increasingly important to enhance generalizability and real world performance in clinical studies. Freenome is developing a blood-based test (MyTectCRC) with the aim of providing a convenient and accessible option for CRC screening. Clinical validation of MyTectCRC test will be supported by PREEMPT CRC, a prospective, observational, multi-center study. The aim of this analysis is to assess the use of community-based recruitment approaches in a diverse inner-city population in Brooklyn, New York. Methods: PREEMPT CRC enrolled subjects aged 45-85 who were at average risk for CRC. To ensure representation of ethnic groups that have historically been difficult to recruit, the study deliberately engaged sites delivering care in diverse communities. Moskowitz Practice recruited from a patient base consisting largely of city workers in Brooklyn, New York, and deployed several patient-focused, ease-of-access methods such as convenient location for colonoscopy (CS) in an ambulatory surgery center, direct patient education from the physician, direct patient support from attentive and engaged site staff, customizable scheduling and screening reminders, and patient-to-patient referrals. Notably, the same approach was used for all study candidates, regardless of the participant’s ethnic/racial representation. Results: Community-based approaches contributed to strong participation from the site’s community in PREEMPT CRC. Importantly, the participants were representative of the local population with 87.4% of the enrollees identified as Black, a group historically underrepresented in oncology studies. The site also successfully enrolled young participants aged 45 to 50 (20.5%) and more females (58.2%) than males. Participants had relatively healthy lifestyles with 91.4% reporting as non-smokers, and 65% reporting no alcohol use. Study participants were highly compliant with study required procedures such as blood collection (100%) and CS (95%). Conclusions: The community-specific methods utilized by the site helped contribute to the diversity enrollment in PREEMPT CRC while recruiting participants that are representative of the local community. Ensuring diversity in clinical studies is the beginning to promoting equity in CRC screening, diagnosis and treatment. A blood-based test, supported by clinical evidence built on data from a diverse and representative population, may provide a convenient and accessible option for CRC screening and potentially increase the screening rate and reduce the CRC burden. Clinical trial information: NCT04369053 .

Rising trend of early-onset colorectal cancer in the US: Incidence and projections to 2030.

e15523 Background: Colorectal cancer (CRC) remains a critical health issue in the United States, particularly notable for its rising incidence in individuals under 55 years. Factors such as lifestyle habits, and genetic predispositions may contribute to pathogenesis while inadequate screening protocols may lead to delayed diagnoses in this younger demographic. Currently, the initial CRC screening guidelines recommend lowering the start age to 45. We seek to provide current data on the US CRC incidence and estimate the burden by 2030. Methods: Using the CDC National Center of Health Statistics database, we queried the incidence rates of CRC from 1999 to 2020. These are reported in Crude rate and age-adjusted rates to standard year 2000 populations per 100,000 person-years. The Autoregressive Integrated Moving Average model was used to predict the projected incidence rate by 2030. R software version 2023.09 was used for analysis. Results: The study identified 3,201,843 CRC cases from 1999-2020, with a notable increase in incidence rates, especially in younger demographics. The largest increase was in the 30-34 age group, with an AAPC of 2.76, followed by the 25-29 and 35-39 age groups, with AAPCs of 2.57 and 2.24, respectively. In contrast, older age groups showed a decline, with the 75-79 age group decreasing from 9.20 to 3.76, and an AAPC of -4.05%. By 2030, early-onset colorectal cancer is expected to rise, particularly in the 40-44 age group (AAPC of 3.26%) and the 35-39 age group (AAPC of 2.92%). The increase is projected mainly in the 25-54 age groups. Conversely, older populations, particularly the 75-79 age group, are projected to see a decrease in incidence rates, from 3.76 to 1.17 per 100,000 by 2030. Conclusions: Our study highlights a significant rise in early-onset CRC, especially in the 25-54 age group, with an increasing projection by 2030 while older age groups are expected to experience a decrease in incidence rates. Consideration should be given to expanding CRC screening in patients younger than 45. [Table: see text]

Changes in US colorectal cancer mortality trends over the past 20 years.

e15543 Background: In the last two decades, colorectal cancer (CRC) mortality has been decreasing in the United States (US). However, the mortality trends for the different subtypes of CRC, including different sides of colon, rectosigmoid, and rectal cancer remain unclear. Methods: We analyzed death certificate data from CDC WONDER from 1999 to 2020. We calculated age-adjusted mortality rates (AAMR) per 100,000 individuals of CRC and its different subtypes and examined the trends over time by estimating the average annual percent change (AAPC) using the Joinpoint Regression Program. Results: From 1999 to 2020, 1,166,099 deaths were attributed to CRC, of which 957,182 deaths (82.08%) were due to colon cancer, 148,862 deaths (12.77%) from rectal cancer, and 60,055 deaths (5.15%) from rectosigmoid cancer. The overall CRC rates decreased significantly from 26.42 (95% CI, 26.20-26.64) to 15.98 (95% CI, 15.84-16.12) per 100,000 individuals, with AAPC of -2.41 (95% CI, -2.55, -2.27). However, the AAMR of rectosigmoid cancer increased significantly from 0.82 (95% CI, 0.78 -0.86) to 1.08 (95% CI, 1.04-1.11) per 100,000 individuals and the AAMR of right-sided colon cancer increased from 0.57 (95% CI, 0.54-0.60) to 0.70 (95% CI, 0.67-0.73) per 100,000 individuals, with AAPC of +1.10 (95%, 0.21-2.00) and +2.06 (95% CI, 0.85 - 3.27) respectively. Men had higher AAMR of CRC than women (23.90 [95% CI, 23.84-23.96] vs. 17.03 [95% CI, 16.99-17.08] per 100,000 individuals). African Americans had the highest AAMR of CRC (26.93 [95% CI, 26.79-27.07]), followed by Whites (19.60 [95%, 19.56-19.64] per 100,000 individuals), American Indians (14.53 [95%, 14.15-14.92] per 100,000 individuals), and Asians (13.04 [95%, 12.89-13.19] per 100,000 individuals). The overall AAMR of CRC decreased for those aged ≥ 50 years but increased significantly from 1.02 to 1.58 per 100,000 individuals for those aged 15-49 years, with an AAPC of +0.75. The AAMR from CRC was the highest in the Midwest (21.04 [95% CI, 20.96-21.12] per 100,000 individuals), followed by the South (20.51 [95% CI, 20.44-20.57]), the Northeast (20.30 [95% CI, 20.22-20.38] per 100,000 individuals), and the West (18.03 [95% CI, 17.95-18.10] per 100,000 individuals). Rural populations had higher AAMR than urban populations (22.40 [95% CI, 22.30-22.49] vs. 19.60 [95%, 19.56-19.64] per 100,000 individuals). Conclusions: Although overall CRC mortality declined, there were rising trends in young-onset CRC, rectosigmoid cancer, and right-sided colon cancer. Disparities persist in terms of sex, race, geographic region, and urbanization level, emphasizing the need for targeted public health measures.

Environmental Levels of Volatile Organic Compounds, Race, and Socioeconomic Markers Correlate with Areas of High Colorectal Cancer Incidence.

Ambient levels of volatile organic compounds (VOCs) released from nearby industrial plants have shown positive associations with increased colorectal cancer (CRC) rates. The objective of this study is to analyze the distribution of CRC in the context of socioeconomic status and its correlation with community environmental data. A retrospective study analyzed CRC patients from 2021 to 2023. The census tracts of the patients' residential addresses were obtained, and CRC rates were calculated for each census tract. Socioeconomic data was gathered on these communities. Environmental VOC measurements were obtained from the National Scale Air Toxics Assessment. All datapoints were compared to statewide levels. Three census tracts in the county had higher CRC cases comparatively. These areas exhibited higher incidence rates and localized clusters of CRC cases, higher distribution of Black or African Americans, lower household incomes, lower home values, and lower educational attainment. VOC measurements in these census tracts had higher levels compared to county and state averages: specifically, 10.68% higher than county and 48.07% higher than state benzene levels (0.52 µg/m3 clusters vs 0.47µg/m3 county vs 0.35 µg/m3 state), 10.84% and 129.15% higher toluene (1.65 µg/m3 vs 1.49 vs 0.72 µg/m3), and 15.64% and 141.87% higher butadiene (0.048 µg/m3 vs 0.041 µg/m3 vs 0.020 µg/m3). This study illustrates a positive correlation between higher ambient exposure to VOCs with increased CRC incidence. These findings underscore the potential interplay of environmental factors, socioeconomic determinants, and environmental injustice when considering strategies to address health disparities and CRC incidence.

Reimagining Colorectal Cancer Screening: Innovations and Challenges with Dr. Aasma Shaukat.

Colorectal cancer (CRC) currently ranks as the third most common cancer and the second leading cause of cancer-related deaths worldwide, posing a significant global health burden to the population. Recent studies have reported the emergence of a new clinical picture of the disease, with a notable increase in CRC rates in younger populations of <50 years of age. The American Cancer Society (ACS) now recommends CRC screening starting at age 45 for average-risk individuals. Dr. Aasma Shaukat's Keynote Conference highlights the critical need for updated screening strategies, with an emphasis on addressing the suboptimal adherence rates and the effective management of the growing burden of CRC. Lowering the adenoma detection screening age can facilitate early identification of adenomas in younger asymptomatic patients, altering the epidemiologic landscape. However, its implications may not be as profound unless a drastic shift in the age distribution of CRC is observed. Currently, various screening options are available in practice, including stool-based tests like multitarget stool DNA (mtDNA) tests, fecal immunochemical testing (FIT), and imaging-based tests. In addition to existing screening methods, blood-based tests are now emerging as promising tools for early CRC detection. These tests leverage innovative techniques along with AI and machine learning algorithms, aiding in tumor detection at a significantly earlier stage, which was not possible before. Medicare mandates specific criteria for national coverage of blood-based tests, including sensitivity ≥ 74%, specificity ≥ 90%, FDA approval, and inclusion in professional society guidelines. Ongoing clinical trials, such as Freenome, Guardant, and CancerSEEK, offer hope for further advancements in blood-based CRC screening. The development of multicancer early detection tests like GRAIL demonstrates a tremendous potential for detecting various solid tumors and hematologic malignancies. Despite these breakthroughs, the question of accessibility and affordability still stands. The ever-evolving landscape of CRC screening reflects the strength of the scientific field in light of an altered disease epidemiology. Lowering screening age along with the integration of blood-based tests with existing screening methods holds great potential in reducing the CRC-related burden. At the same time, it is increasingly important to address the challenges of adaptation of the healthcare system to this change in the epidemiologic paradigm.

Colorectal cancer screening with virtual colonography

Since 2003, adecline in the age-standardized incidence rates of colorectal cancer (CRC) has been observed in Germany. Nonetheless, one in eight cancer cases still affects the colon or rectum. The prognosis has improved, with the relative 5‑year survival rate for CRC being approximately 65%. This positive trend is probably aresult of preventive measures introduced over the last 20years. This could be further improved, however, as CRC can not only be detected early but in almost all cases also prevented through the identification of benign precursors. Less than half of all eligible individuals participate in screening via colonoscopy. This implies that further, possibly even imaging, screening test methods should be explored and offered. Studies have reported that virtual colonography techniques have acomparable accuracy to endoscopy of about 90% for polyp sizes larger than 5 mm. The data for computed tomography (CT) is more extensive than for magnetic resonance imaging (MRI). Significant challenges are posed however by the fact that in Germany CT colonography (CTC) is not considered aviable screening option due to radiation protection concerns, and MRI screening is not an established screening method. Radiologists should be familiar with classification using the CT Colonography Reporting and Data System (C-RADS), which uses criteria such as CT density, morphology, size, and location for classification. C‑RADS classification follows the categories: C0 (inadequate study), C1 (normal), C2a (indeterminate), C2b (benign), C3 (suspicious), and C4 (malignant), as well as extracolonic categories E1/2 (no clinically significant findings), E3 (likely insignificant findings), and E4 (likely significant findings).

Single-cell transcriptomics of colorectal cancer metastases identifies enrichment for a therapeutically targetable population of TREM2+ macrophages in peritoneal metastases.

Abstract Colorectal cancer (CRC) is recognized as the third most common cancer and the second leading cause of cancer-related mortality globally. The primary driver behind this mortality is metastatic disease, which significantly worsens the prognosis for CRC patients. Over the past decade, there has been a modest improvement of only 2% in the 5-year survival rate for metastatic CRC (mCRC). To improve our understanding of the cellular composition in mCRC tumors, we performed single-cell RNAseq (scRNAseq) on matched primary colorectal tumors, metastases to the lung, liver, and peritoneum, and malignant ascites from 14 patients. Tumor-associated macrophages (TAMs) were found to be one of the most abundant populations across all samples and TAMs from metastases had increased expression of M2-like alternative activation markers relative to primary tumors, suggesting that TAMs in mCRC are immunosuppressive. Gene co-expression analysis identified a signature of lipid handling containing genes linked to lipid transport, such as APOE, FABP5, PLTP, and CD9, and genes coding for the scavenger receptors CD36, MSR1, MARCO, and TREM2. Consistent with transcriptomics, the majority of CD11b+CD68+ TAMs from resected liver and peritoneal metastases had high TREM2 expression by flow cytometry. In a mouse model of peritoneal mCRC, treatment with anti-TREM2 decreased CD11b+F4/80+ TAMs and increased CD8+ effector T cells, suggesting that TREM2 may be an effective target for immunotherapy in mCRC.

Evaluation of the “Burgenland PREvention trial of colorectal cancer Disease with ImmunologiCal Testing” (B-PREDICT)—a population-based colorectal cancer screening program

BackgroundThe colorectal cancer (CRC) screening program B-PREDICT is a population based invited two stage screening project using a faecal immunochemical test (FIT) for initial screening followed by a colonoscopy for those with a positive FIT. B-PREDICT was compared with the opportunistic screening colonoscopy (OPP-COL), performed in course of the nationwide screening program.MethodsWithin B-PREDICT all residents of the Austrian federal state Burgenland, aged between 40 and 80 are annually invited to FIT testing. All individuals who underwent initial colonoscopy in Burgenland between 01/2003 and 12/2014, were included in this study. Individuals from the FIT-triggered invited screening program B-PREDICT were compared with those from the non-FIT triggered OPP-COL.Results15 133 individuals from B-PREDICT were compared to 10 045 individuals with OPP-COL. CRC detection rates were 1.34% (CI-95%, [1.15; 1.52]) in B-PREDICT compared to 0.54% in OPP-COL (95%-CI, [0.39; 0.68] p < 0.001). The decrease in the age standardized incidence rates of CRC was more pronounced in the population screened with FIT than in the general population screened with colonoscopy. Changes in incidence rates per year were -4.4% (95%-CI, [-5.1; -3.7]) vs. -1.8% (95%-CI, [-1.9; -1.6] p < 0.001).ConclusionsB-PREDICT shows a two-fold higher detection rate of CRC as well as HRA compared to OPP-COL.

Is the incidence rate of colorectal cancer increasing in Mozambique?

Colorectal cancer (CRC) is a significant global health concern, ranking as the third most common cancer and the second leading cause of cancer-related deaths. However, in Africa, CRC is the fifth most common invasive malignancy. Limited data hinder our understanding of the evolving burden of CRC in sub-Saharan Africa. This study explores CRC trends in Mozambique, utilising data from population-based oncological registries. CRC data were gathered from Beira and Maputo population-based cancer registries, along with supplementary information from pathology-based and hospital-based registries. Comparative analyses were performed across different time periods, focusing on trends and epidemiological characteristics. Incidence rates of CRC in Maputo and Beira were relatively low historically. However, data from recent years showed an increase, especially in age groups above 50. Analyses from pathology-based and hospital-based registries affirmed the rising trend. The age-standardised incidence rate in Maputo (2015-2017) was 3.17 for males and 2.55 for females. Beira exhibited increasing rates between 2009 and 2020, particularly in individuals aged 50 and above. The study reveals an emerging burden of CRC in Mozambique, challenging the perception of low incidence. The rising trend underscores the necessity for tailored interventions, emphasizing early diagnosis, preventive strategies, and investments in healthcare infrastructure to address the increasing CRC burden in the region.

Trends in colorectal cancer screening compliance and incidence among 60- to 74-year-olds in China.

Compliance with colonoscopy among elderly individuals participating in colorectal cancer (CRC) screening programs is unsatisfactory, despite a high detection rate of bowel-related diseases. In this study, our aim was to analyze the impact of risk factors on the trends of compliance and detection rates in colonoscopy among high-risk individuals aged 60-74. A retrospective study was conducted on the high-risk individuals aged 60-74 participating in the 2021 CRC screening program in Tianjin, China. Logistic regression analyses, including both univariate and multivariate analyses, were performed to explore the impact of different risk factors on colonoscopy compliance among the high-risk individuals. Besides, the study investigated the influence of various risk factors on the detection rates of bowel-related diseases among the high-risk individuals who underwent colonoscopy. A total of 24,064 high-risk individuals were included, and 5478 individuals received a free colonoscopy, with an overall compliance of 22.76%. Among them, the adenoma detection rate was 55.46%. Males and individuals with a positive FIT had high compliance and detection rates for CRC, advanced adenomas (AA), advanced colorectal neoplasia (ACN), and colorectal neoplasm (CN). Individuals aged 70-74 were associated with low compliance but high CRC, ACN, and CN detection rates. Individuals who reported a history of chronic constipation, bloody mucous, and CRC in first-degree relative showed high compliance but no significantwere associated with the detection rates of CRC, AA, and CN. This study reported several risk factors associated with the screening behaviors for CRC. Patterns and trends in CRC, AA, ACN, and CN compliance and detection rates correlate with risk factors.

RAS-Selective Lethal 3-Induced Ferroptosis Promotes the Antitumor Efficiency of Anti-Programmed Cell Death Protein 1 Treatment in Colorectal Cancer.

Anti-programmed cell death protein 1 (PD-1) treatment has exhibited clinical benefits in colorectal cancer (CRC). However, the low response rate of CRC to immunotherapy is an urgent problem that needs to be solved. MC-38 tumor cells was challenged subcutaneously in the flank of 7-week-old male C57BL/6 mice. The mice were randomly divided into 3 groups, and 200µg/mouse anti-PD-1 antibody and 100 mg/kg RAS-Seletive Lethal 3 (RSL) or phosphate buffer saline (PBS) were intraperitoneally injected every 2 days. The expression of oxidative stress and ferroptosis-related genes was measured by Western blotting, real-time reverse transcription-polymerase chain reaction, Prussian blue staining, and enzyme-linked immunosorbent assay. Anti-PD-1 treatment-unresponsive tumors showed stronger immunosuppression than responsive tumors. Notably, the responsive tumors showed higher levels of H2O2 and reactive oxygen species, both of which could impair the antitumor effect of cytotoxic CD8+ T cells. The anti-PD-1 treatment-responsive tumors showed a higher expression of pro-ferroptosis genes and Fe2+ accumulation than those of anti-PD-1 nonresponsive tumors, indicating the potential role of ferroptosis in the efficacy of anti-PD-1 treatment. In MC-38 syngeneic tumor model, (1S, 3R)-RSL3 (RSL), a glutathione peroxidase 4 inhibitor, effectively promoted the antitumor effect of anti-PD-1 treatment in vivo. However, anti-PD-1 treatment did not affect the levels of ferroptosis-related genes in tumor model. Mechanistically, RSL treatment significantly upregulated the frequency of proliferating (ki67+) and cytotoxic (GZMB+) CD8+ T cells. Furthermore, the frequency of tumor neoantigen-specific interferon (IFN)-γ CD8+ T cells showed a significant increase after RSL plus anti-PD-1 treatment. RSL may be a promising drug for potentiating the antitumor efficiency of anti-PD-1 treatment in CRC.

A Novel Approach in Elucidating the Interaction of Ecology, Biology and Social (Eco-bio-social) Factors with Serum Metabolites and Its Pathway among Polyps and Colorectal Cancer: A Study Protocol

The increasing number of colorectal cancer (CRC) incidences and mortality rates have caused an increasing burden on the healthcare system of the involved countries. This will impact the important economic components as a burden including direct medical care and non-medical costs and have caused productivity losses among patients and caregivers. Early diagnosis is important to help in reducing mortality rates of CRC and enhancing disease treatments. Besides genetic pathways, lifestyle imbalance and environmental factors also are reported as the main causes of CRC.However, most of the previous studies only focused on one factor at a time which limit the understanding of how these factors could be manipulated in the disease biomarkers finding. Hence, this study helps to build a novel protocol to provide a better insight into the effects of the ecology, biology, and social factors on the differential level of a polyp and CRC serum metabolites that could potentially be used to distinguish patients with polyp or CRC. The finding of the study could serve as a potential biomarker that could be used in the development of new screening tools to enhance early screening of polyps and CRC.

How have US colorectal cancer mortality trends changed in the past 20 years?

In the last two decades, colorectal cancer (CRC) mortality has been decreasing in the United States. However, the mortality trends for the different subtypes of CRC, including different sides of colon, rectosigmoid, and rectal cancer remain unclear. We analyzed the mortality trends of different subtypes of CRC based on Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research data from 1999 to 2020. We calculated age-adjusted mortality rates (AAMR) per 100,000 individuals and examined the trends over time by estimating the average annual percent change (AAPC) using the Joinpoint Regression Program. Our study shows that the overall CRC rates decreased significantly from 26.42 to 15.98 per 100,000 individuals, with an AAPC of -2.41. However, the AAMR of rectosigmoid cancer increased significantly from 0.82 to 1.08 per 100,000 individuals, with the AAPC of +1.10. Men and Black individuals had the highest AAMRs respectively (23.90 vs. 26.93 per 100,000 individuals). The overall AAMR of CRC decreased for those aged ≥50 years but increased significantly from 1.02 to 1.58 per 100,000 individuals for those aged 15-49 years, with an AAPC of +0.75. Rural populations had a higher AAMR than the urban populations (22.40 vs. 19.60 per 100,000 individuals). Although overall CRC mortality declined, rising trends in young-onset CRC and rectosigmoid cancer warrant attention. Disparities persist in terms of sex, race, and geographic region, and urbanization level, emphasizing the need for targeted public health measures.

Abstract 4871: Colorectal cancer incidence and overall survival by race, stage, and age: A SEER database analysis, 2009-2020

Abstract Introduction: In the United States, colorectal cancer (CRC) is the fourth most common cancer and the second leading cause of cancer-related deaths. Although incidence rates of CRC have been decreasing overall, recent studies suggest a shift in demographics, specifically an increase in the number of new CRC cases among younger individuals and a higher incidence among those who identify as non-Hispanic Native American/Alaska Native. To examine the latest trends in incidence and overall survival (OS) among adults with CRC in the United States, we conducted an observational study using the Surveillance, Epidemiology, and End Results (SEER) Program database. Methods: Patients aged ≥18 years with newly diagnosed CRC between January 1, 2009, and December 31, 2020 were identified in the SEER 17 database. Age-adjusted incidence rates for CRC were calculated by race/ethnicity and age groups (18-49, 50-64, and ≥65 years) from 2009 to 2020. Kaplan-Meier curves were generated to examine 5-year OS by race/ethnicity, stage, and age groups. Results: There were 429,218 CRC cases identified with a median age of 67 years. Most were male (52.4%) with stage 0-II CRC (51.4%). Most patients identified as non-Hispanic White (66.3%), followed by non-Hispanic Black (11.5%), non-Hispanic Asian/Pacific Islander (8.9%), non-Hispanic Native American/Alaska Native (0.7%), and Hispanic of any race (12.7%). The age-adjusted incidence rate between 2009 and 2020 was 51.9 per 100,000 persons; incidence decreased from 59.5 per 100,000 persons in 2009 to 44.2 per 100,000 persons in 2020, with male patients having a higher incidence rate than female patients. By 2020, non-Hispanic Native American/Alaska Native patients had the highest incidence rate (54.5 per 100,000 persons) followed by non-Hispanic Black patients (50.6 per 100,000 persons). CRC incidence rates increased slightly for age &amp;lt;50 years (10.5 to 12.9 per 100,000 persons) and decreased for ages 50-64 (74.6 to 63.9 per 100,000 persons) and ≥65 years (222.4 to 136.1 per 100,000 persons). Non-Hispanic Black patients (53%), age ≥65 years (47%), and those with stage III-IV CRC (41%) had a lower 5-year OS from 2015 to 2019 compared to patients who were non-Hispanic White (57%), aged 50-64 (68%) and &amp;lt;50 years (70%), and with stage 0-II CRC (77%). Conclusion: Our results confirm a slight increase in CRC incidence among younger (&amp;lt;50 years) individuals over the 2009-2020 time period. Patients who were non-Hispanic Native American/Alaska Native had the highest CRC incidence rate and patients who were non-Hispanic Black had the poorest OS. Targeted preventative efforts such as CRC screening programs in addition to improved access to care/treatment may be needed to reduce the number of new cases and improve outcomes among historically underserved groups. Citation Format: Alicia C. McDonald, Seongjung Joo, Jiemin Ma, Mayur M. Amonkar, Changxia Shao, Kaushal Desai, Anne C. Deitz. Colorectal cancer incidence and overall survival by race, stage, and age: A SEER database analysis, 2009-2020 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4871.

Abstract 4872: Elevated colorectal cancer incidence among American Indian/Alaska Native persons in Alaska compared to other populations worldwide

Abstract Background: Colorectal cancer (CRC) is a leading cancer worldwide. Incidence varies greatly by country and racial group. We present recent CRC incidence and mortality rates among American Indian/Alaska Native (AI/AN) persons in Alaska and compare them to rates among other racial groups in Alaska and AI/AN persons in other regions of the United States, and to published CRC incidence rate estimates for other countries around the world. Methods: To calculate CRC incidence in the United States, we used U.S. Cancer Statistics data, which includes cancer registry data from the Centers for Disease Control and Prevention’s (CDC) National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program. Cancer data for AI/AN persons in Alaska came from the Alaska Cancer Registry as well as the Alaska Native Tumor Registry. Death data came from the CDC’s National Death Index, which was linked with the Indian Health Service patient registry database to address race misclassification in AI/AN populations, to create the United States Cancer Statistics American Indian and Alaska Native Mortality Database. This database was used to calculate CRC mortality rates for AI/AN persons in this study. Rates were age-adjusted using the World Health Organization’s World Standard Population (2000-2025), so that rates for AI/AN persons in the United States could be more comparable to rates that have been estimated for countries around the world. Estimates of worldwide CRC incidence came from the International Agency for Research on Cancer Global Cancer Observatory GLOBOCAN 2020 database. Results: AI/AN persons in Alaska (males and females combined) had the highest CRC incidence rate (58.4 per 100,000 people) in the year 2020, when compared to AI/AN persons in every other region of the United States. Within Alaska, AI/AN persons had a higher CRC incidence rate than persons of any other racial group. When compared with published CRC incidence rates worldwide, the rate for AI/AN persons in Alaska was higher than the rates reported for any country in the world in 2020. The country with the highest recorded CRC incidence rate in 2020 was Hungary (45.3 per 100,000 people). AI/AN persons in Alaska also had the highest CRC mortality rate (27.1 per 100,000 people) in 2020. Worldwide, the country with the highest recorded CRC mortality rate in 2020 was Slovakia (21.0 per 100,000 people). Conclusions: This review of CRC incidence and mortality rates from populations in the US and worldwide showed that AI/AN persons in Alaska had the highest documented incidence and mortality rates of CRC in the world in 2020. Health systems serving AI/AN persons in Alaska could implement policies and interventions that support colorectal cancer screening, to reduce the burden of this preventable disease. Citation Format: Donald Haverkamp, Diana Redwood, Elena Roik, Stephen Vindigni. Elevated colorectal cancer incidence among American Indian/Alaska Native persons in Alaska compared to other populations worldwide [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4872.

Abstract 4787: Preference for multi-target stool DNA for colorectal cancer screening among Alaska Native people in rural/remote communities

Abstract Background: The Alaska Tribal Health System is working on increasing colorectal cancer (CRC) screening rates among Alaska Native people, who have the highest CRC rates in the world. Most remote Alaska Native communities are not connected to the road system, which severely limits access to screening colonoscopy. As part of a clinical trial, Alaska Native patients were offered either colonoscopy or the at-home multi-target stool DNA test (mt-sDNA; Cologuard®). Patients had never been offered mt-sDNA before and it was unknown what they would think about the new test option. Both tests were provided at no cost to patients. Methods: From April 2022 to July 2023, 194 patients who chose mt-sDNA for screening received a follow-up phone survey asking whether they were aware that they could have had colonoscopy instead, their reasons for choosing mt-sDNA, and the factors influencing their choice of mt-sDNA over colonoscopy. Patients answered the survey before receiving results of their mt-sDNA test in order to capture initial screening test preferences. Results: A total of 115 (59%) Alaska Native patients participated in the survey; 56% men and 44% women. About 70% were ages 45 to 60 years while the remaining 30% were 61 to 75 years old. The majority (80%) were aware that they had the option to undergo colonoscopy for CRC screening instead of mt-sDNA. Key themes for mt-sDNA preference included not having to travel, less time commitment, and greater convenience. Many patients expressed financial concerns arising from the costs of air travel and accommodation required to access screening colonoscopy even though the procedure itself was covered. Additionally, patients highlighted existing obligations such as childcare and work responsibilities which made the use of mt-sDNA at home more appealing. Many respondents also shared negative perceptions of colonoscopy procedure including fear, embarrassment, and discomfort as reasons why they preferred mt-sDNA instead. Conclusions: These findings demonstrate the multifaceted factors influencing the preference for at-home mt-sDNA CRC screening among Alaska Native individuals. Challenges such as limited access to medical facilities, financial burdens, and personal commitments have significant bearing on the screening decision-making process. Moreover, the emotional aspect of fear and discomfort associated with colonoscopy plays a role in shaping these preferences. CRC screening programs need to be aware of patient needs and preferences when deciding which screening methods to offer to increase screening rates and result in improved colorectal health outcomes. Citation Format: Diana Redwood. Preference for multi-target stool DNA for colorectal cancer screening among Alaska Native people in rural/remote communities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4787.

Mutational profile evaluates metastatic capacity of Chinese colorectal cancer patients, revealed by whole-exome sequencing

Colorectal cancer (CRC) is the third most common cancer and the prevalence rate of CRC is increasing in the China. In this study, whole-exome sequencing (WES) was performed on primary tissues of 47 CRC Chinese patients including 22 metastatic and 25 non-metastatic patients. By comparison with data from western colorectal cancer patients in the Cancer Genome Atlas (TCGA), we identified a number of genes that are more likely to be mutated in Chinese colorectal cancer patients, such as MUC12, MUC12, MUC2, MUC4, HYDIN and KMT2C. Interestingly, MUC family genes including MUC12, MUC2 and MUC4, have mutation rates of >20%, while the mutation frequency was extremely low in western colorectal cancer patients, which were <3% in TCGA and 0% in Memorial Sloan Kettering Cancer Center (MSKCC). We detected metastasis-specific mutated genes including TCF7L2, MST1L, HRNR and SMAD4, while MUC4, NEB, FLG and RFPL4A alteration is more prevalent in the non-metastasis group. Further analysis reveals mutation genes in metastasis group are more focus in the Wnt and Hippo signaling pathway. APC, SMAD4 and TCF7L2 accounted for the major genetic abnormalities in this pathway. In conclusion, this study identified the unique characteristics of gene mutations in Chinese patients with colorectal cancer, and is a valuable reference for personalized treatment in Chinese CRC patients.

Population-based screening for colorectal cancer in Wuhan, China.

https://www.chictr.org.cn/showproj.html?proj=192838, identifier ChiCTR2300070520.