Colorectal cancer (CRC) is a common malignancy and cause for death around the world. In India, it ranks as the fourth most incident cancer in both sexes, with 64,863 cases and 38,367 deaths in 2022. With such high mortality, CRC survival in India is way lesser than that of developed countries. While western countries are facing an overall decline in CRC incidence, various regions in India are seeing an increasing trend. Within India, urban regions have markedly higher incidence than rural. Risk factors include consumption of red and processed meat, fried and sugary food, smoking and alcohol, comorbidities such as obesity, diabetes and inflammatory bowel disease (IBD), family history of CRC, adenomas and genetic syndromes, radiation exposure, pesticides and asbestos. Consumption of nutrient-rich well-balanced diets abundant in vegetables, dairy products, whole grains, nuts and legumes combined with physical activity are protective against CRC. Besides these, metformin, aspirin and micronutrient supplements were inversely associated with the development of CRC. Since a considerable proportion of CRC burden is attributed to modifiable risk factors, execution of population level preventive strategies is essential to limit the growing burden of CRC. Identifying the necessity, in this review, we explore opportunities for primary prevention and for identifying high-risk populations of CRC to control its burden in the near future.

Oral microbes detected in feces have been associated with colorectal cancer (CRC) in cross-sectional studies. This study investigated the prospective associations between the oral microbiome and incident CRC in the Agricultural Health Study (AHS), National Institutes of Health-AARP (NIH-AARP) Diet and Health Study, and Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.

Individuals with oral samples collected before incident CRC diagnoses were identified in the AHS (N = 331), NIH-AARP (N = 249), and PLCO (N = 446) and compared with referent subcohorts (N = 3431). The V4 region of the 16S ribosomal RNA gene was sequenced from oral wash DNA, and the data were processed with QIIME2. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall CRC and by anatomic subsite (i.e., proximal colon, distal colon, and rectum) were estimated with Cox proportional hazards models with adjustment for potential confounders by cohort and then meta-analyzed.

Overall, no associations were found between microbial characteristics and CRC risk. However, associations were observed with alpha and beta diversity indices and individual genera in analyses stratified by anatomic subsite. For instance, the presence of Olsenella was strongly positively associated with distal colon cancer risk (HR, 2.16; 95% CI, 1.59-2.95), whereas the presence of Prevotella 2 was positively associated with rectal cancer risk (HR, 1.68; 95% CI, 1.14-2.46).

This large study of the prospective association between the oral microbiome and CRC risk showed numerous site-specific associations, including multiple associations with distal colon and rectal cancer risk.

The tumor microenvironment is a dynamic and complex three-dimensional network comprising the extracellular matrix and diverse non-cancerous cells, including fibroblasts, adipocytes, endothelial cells and various immune cells (lymphocytes T and B, NK cells, dendritic cells, monocytes/macrophages, myeloid-derived suppressor cells, and innate lymphoid cells). A constantly and rapidly growing number of studies highlight the critical role of these cells in shaping cancer survival, metastatic potential and therapy resistance. This review provides a synthesis of current knowledge on the modulating role of the cellular microenvironment in cancer progression and response to treatment.

The incidence of early-onset colorectal cancer is increasing, but in Europe this growth shows a heterogeneous pattern in different countries and regions.

Patients from six countries who participated in the Global Early-Onset COlorectal Cancer DatabasE (GEOCODE)-Europe group were included. The inclusion criteria were patients with colorectal adenocarcinoma diagnosed between 18 and 49 years of age, between January 2010 and December 2017, with at least 3 years of follow-up. Patients with inherited colorectal cancer syndromes were excluded.

A total of 851 patients were included with almost equal sex distribution, most were diagnosed at age 39 years or older and 42% of patients were overweight or obese. Diagnoses were predominantly at later stages (62.5% stage III-IV) and tumours were predominantly located in the distal colon (76.9% left colon and rectum). Comparative analysis between countries demonstrated that the UK had a younger age at diagnosis and the Italian cohort had a higher prevalence of being overweight or obese. Patients from Luxembourg had more advanced stage diagnoses and those from The Netherlands had more polyps. Patients from the UK had a greater family history of colorectal cancer. Comparison of Mediterranean versus non-Mediterranean countries showed significant differences in the age at diagnosis and body mass index. The prevalence of early-onset colorectal cancer over the age of 40 years in Mediterranean versus non-Mediterranean countries was 71.4% versus 62.1% (P = 0.002), and early-onset colorectal cancer was diagnosed at a more advanced stage in Mediterranean countries versus non-Mediterranean countries (65.3% versus 54.7%; P = 0.033). Family history of colorectal cancer in a first-degree relative was more common in non-Mediterranean versus Mediterranean countries (19.1% versus 11.4%; P < 0.001).

This study highlights significant geographical disparities in the clinical, pathological and familial features of early-onset colorectal cancer across European countries.

The existing evidence has shown a positive association between alcohol consumption and an increased risk of colorectal cancer (CRC). However, the evidence is primarily based on studies of CRC in all ages, and the role of alcohol in early onset colorectal cancer (EOCRC) remains to be determined. The aim of this study was to investigate an association between the increasing incidence of EOCRC and alcohol consumption.

We systematically searched PubMed, EMBASE, Cochrane and Web of Science up to June 2024 for studies that evaluated the association of alcohol intake with EOCRC risk and report specific results (e.g. relative risk, OR or hazard ratio and corresponding 95% CI). Based on the varying designs of the included studies, the corresponding effect values were extracted and categorized into high alcohol consumption and low alcohol consumption groups; a random-effects model was adopted to estimate the pooled effect sizes for analysis. Furthermore, subgroup analyses and publication bias assessments were conducted.

Three cohort studies and eight case-control studies were eligible and included. The results were pooled in meta-analyses, which yielded a heightened risk of EOCRC for increased alcohol intake (OR = 1.56, 95% CI 1.28-1.89, I2 = 89.3%). In the subgroup analysis, no significant differences were found in the association between alcohol consumption and the risk of developing EOCRC across gender, location or tumour site. The results of sensitivity analysis and publication bias indicated that the conclusion was robust.

This meta-analysis provides possible evidence for an association between alcohol consumption and risk of EOCRC. More research is needed in the future to confirm these findings.

Rates of colorectal cancer (CRC) screening in the United States continue to fall short of guideline-recommended benchmarks. Challenges to increasing CRC screening include racial disparities, barriers at multiple levels of the health care system, and inadequate completion of 2-step screening. With new options for CRC screening and employment of programmatic strategies for screening by physicians, patients will have more opportunities to initiate and complete testing, which can ultimately improve CRC detection and prevention. This article highlights the current state of and optimal approach to CRC screening.

The incidence of early-onset colorectal cancer among the young (<50 years) has been reported to have risen in last decades. This retrospective study aimed to investigate the characteristics of early-onset rectal cancers (EO-RCs) and potential changes in proportion of EO-RCs, and further to report the mortality and recurrence rates of EO-RCs.

In the years 2007-2021, 2557 rectal cancer (RC) patients were operated in Helsinki University Hospital and of them 147 were 18-49 years old. Cumulative overall survival (OS), disease-specific survival, and disease-free survival were calculated using the Kaplan-Meier analysis.

The percentual amount of the EO-RCs varied between 2.5% and 11.3% annually and there was no perceivable trend. Majority were adenocarcinomas (98.7%), of which 8.8% were mucinous. Predisposing factors such as Lynch syndrome, polyposis, or ulcerative colitis were seen in 26 patients (17.7%) and in 10 of 22 patients (45.5%) under 35 years. The cumulative 5-year OS was 91.9% in stage I, 93.3% in stage II, 86.7% in stage III, and 50.0% in stage IV disease. Metastatic recurrence was found in 22 cases (18.4%) and local recurrence in 8 patients (5.4%) and 6 patients had both.

In our cohort of 147 EO-RC patients, OS was good and the clinical course did not seem to differ much from the course of RC in general population.

Rising rates of early-onset colon cancer (EOCC) present challenges in deciding how to optimally treat patients. Although standard of care for stage II CC is surgical resection, adding chemotherapy for high-risk disease, evidence suggests treatment selection may differ by age. We investigated whether adjuvant chemotherapy (AC) administration rates differ between patients with early- and later-onset stage II CC.

Data originated from the nationwide Flatiron Health electronic health record (EHR)-derived deidentified database spanning January 1, 2003, to August 1, 2021. Adults with stage II CC were grouped as age 18-49 years (EOCC) and those age 50 years or older (later-onset colon cancer [LOCC]). Demographics, Eastern Cooperative Oncology Group score, tumor stage and site, and chemotherapy were included. Primary outcomes included rates of AC administration by age and ethnicity; secondary outcomes included overall survival (OS) and time to metastatic disease (TTMD). Univariate and multivariable logistic regression models evaluated relationships between chemotherapy administration, age, and ethnicity, adjusting for significant covariates.

One thousand sixty-five patients were included. Median age of patients with EOCC was 45.0 years versus 69.0 years for patients with LOCC. Adjusted multivariate analysis showed patients with EOCC received AC significantly more often than patients with LOCC. Non-Hispanic patients received AC at significantly lower rates than Hispanic patients in both cohorts. Subanalysis of stage IIA patients showed that patients with EOCC were more likely to receive AC than patients with LOCC. No significant differences in OS or TTMD were observed by age regardless of AC administration in stage II overall; however, patients with stage IIA EOCC receiving AC had significantly longer TTMD than those not receiving AC.

AC was given preferentially in stage II EOCC, even in stage IIA, despite deviation from guidelines. This may expose low-risk patients to unnecessary toxicities and suggests bias toward treating younger patients more aggressively, despite unclear evidence for better outcomes.

Emerging research suggested a potential role of immune cells in colorectal cancer (CRC) development. However, the causal relationship between immune phenotypes and CRC remains elusive. Hence, this two-sample Mendelian randomization (MR) study aimed to explore the causal association.

In this study, a bidirectional, two-sample MR analysis and multivariate MR was conducted, leveraging public genetic data. Four types of immune phenotypes were employed. A comprehensive sensitivity analysis was carried out to validate the robustness, heterogeneity, and horizontal pleiotropy of the results, with Bonferroni correction applied for accurate interpretation.

It was revealed that four immune cell phenotypes were significantly associated with CRC risk. Specifically, lymphocyte % leukocyte in the T-cell/B-cell/NK-cell (TBNK) group (odds ratio (OR) = 1.0013, 95% confidence interval (CI): 1.0005-1.0017, P = 0.0003, PBonferroni = 0.011) and CD3 on CM CD8br in the maturation stages of T cell group (OR = 1.0014, 95% CI: 1.0006-1.0022, P = 0.0007, PBonferroni = 0.023) were positively correlated with the risk of CRC. Conversely, DN (CD4-CD8-) %leukocyte in the TBNK group (OR = 0.9990, 95% CI: 0.9984-0.9997, P = 0.0020, PBonferroni = 0.063) and herpesvirus entry mediator (HVEM) on CD8br in the maturation stages of T cell group (OR = 0.9989, 95% CI: 0.9982-0.9997, P = 0.00431, PBonferroni = 0.137) exhibited a negative association with the risk of CRC. This study did not detect any statistically significant impact of CRC on immune phenotypes.

This study inferred an association between immune cells and CRC risk. Nevertheless, further clinical and experimental studies are warranted to validate these findings and elucidate the underlying mechanisms.

Background and Objectives: Early-onset colorectal cancer (EO-CRC) has become a significant public health concern due to its alarming rise in incidence and the poor prognosis associated with this disease. The aim of our study was to identify epidemiological, clinical, and paraclinical characteristics that could explain the more aggressive evolution of EO-CRC compared to late-onset colorectal cancer (LO-CRC). Materials and Methods: We conducted a retrospective study over a two-year period, including 204 patients diagnosed with colorectal cancer (CRC). The patients were divided into two subgroups: those with EO-CRC and those with LO-CRC. Statistical analysis was performed using IBM SPSS Statistics, Version 29.0. Results: EO-CRC was identified in 11.3% of the patients included in the study. Compared to LO-CRC patients, EO-CRC patients exhibited a tendency for more distal tumor localization and a stenotic endoscopic appearance (43.5% vs. 29.3%). Regarding histopathological diagnosis, EO-CRC patients demonstrated a higher proportion of the mucinous histologic subtype (34.8% vs. 14.4%) and a significantly greater percentage of poorly differentiated tumors (39.1% vs. 14.5%; p = 0.010). Immunohistochemical results, available for a limited number of patients, revealed higher CDX2 positivity in LO-CRC patients (p = 0.012) and higher HER2 positivity in EO-CRC patients (p = 0.002). Smoking (p = 0.006) and hypertension (p = 0.002) were more prevalent in EO-CRC patients than in LO-CRC patients. Conclusions: Patients with EO-CRC exhibit distinct histopathological and molecular characteristics compared to those with LO-CRC, which may contribute to their poorer prognoses. The higher prevalence of the mucinous histological subtype, poor tumor differentiation, increased HER2 expression, and reduced CDX2 expression suggest potential molecular pathways driving the aggressive nature of EO-CRC. These findings highlight the need for tailored screening strategies and personalized therapeutic approaches in younger CRC patients. Future studies should further investigate the underlying mechanisms and potential biomarkers that could guide early diagnoses and targeted treatments.

Colorectal cancer (CRC) incidence and mortality in those aged 50 years and above have decreased over the past 2 decades. However, there is a rising incidence of CRC among individuals under 50 years of age, termed early-onset colorectal cancer (EOCRC). Patients with EOCRC are diagnosed at an advanced stage and may be in more psychosocial, emotional, and financial distress.

Our study examined the epidemiological shifts in CRC in Singapore, a multiethnic country.

CRCs diagnosed at age 20 years and above were identified from the Singapore Cancer Registry (SCR) from 1968 to 2019. Patient characteristics included gender, ethnicity, and age of CRC diagnosis. Population information was obtained from the Department of Statistics Singapore (SingStat). Age-specific incidence rates (ASRs) and age-standardized incidence rates (ASIRs) were calculated. The cohort was divided into 3 age groups: 20-49, 50-64, and ≥65 years. Temporal trends in incidence rates were modeled with joinpoint regression. Birth cohort models were fitted using the National Cancer Institute (NCI) age-period-cohort analysis tool. Cancer-specific survival analysis was performed with the Cox proportional hazards model.

In total, 53,044 CRCs were included, and 6183 (11.7%) adults aged 20-49 years were diagnosed with EOCRC. The ASR of EOCRC rose from 5 per 100,000 population in 1968 to 9 per 100,000 population in 1996 at 2.1% annually and rose to 10 per 100,000 population in 2019 at 0.64% annually. The ASR for CRC among adults aged 50-64 years rose at 3% annually from 1968 to 1987 and plateaued from 1987, while the ASR for adults aged 65 years and above rose at 4.1% annually from 1968 to 1989 and 1.3% annually from 1989 to 2003 but decreased from 2003 onwards at 1% annually. The ASR of early-onset rectal cancer increased significantly at 1.5% annually. There was a continued rise in the ASR of EOCRC among males (annual percentage change [APC] 1.5%) compared to females (APC 0.41%). Compared to the 1950-1954 reference birth cohort, the 1970-1984 birth cohort had a significantly higher incidence rate ratio (IRR) of 1.17-1.36 for rectal cancer, while there was no significant change for colon cancer in later cohorts. There were differences in CRC trends across the 3 ethnic groups: Malays had a rapid and persistent rise in the ASR of CRC across all age groups (APC 1.4%-3%), while among young Chinese, only the ASR of rectal cancer was increasing (APC 1.5%). Patients with EOCRC had better survival compared to patients diagnosed at 65 years and above (hazard ratio [HR] 0.73, 95% CI 0.67-0.79, P<.001) after adjusting for covariates.

The rise in the incidence of rectal cancer among young adults, especially among Chinese and Malays, in Singapore highlights the need for further research to diagnose CRC earlier and reduce cancer-related morbidity and mortality.

Colorectal cancer metastasis is governed by a variety of chemical and mechanical signaling that are largely influenced by cancer-associated fibroblasts (CAFs) in the tumor microenvironment. Here, we deconvolute the chemical from mechanical signaling in the case of the colon cancer cell line HCT-116 and CAFs. We examined three chemoattractants (CXCL12, TGF-β, and activin A) which allegedly are secreted by CAFs and induce HCT-116 cell migration. None of the chemoattractants tested resulted in enhanced migration of HCT-116 in a 2D transwell assay, at low cell density. Similarly, CAF-conditioned media also did not lead to enhanced HCT-116 migration, while CAFs co-cultured in the transwell assay did lead to increased HCT-116 migration. This result suggests that either high cell densities are required for chemotaxis, and/or a reciprocal two-way signaling network between CAFs and HCT-116 is necessary to induce chemotaxis. Surprisingly, we find that HCT-116 cells exhibit enhanced migration along the axis of mechanical stress in a 3D collagen matrix, at very high cell densities. This migration is independent of whether the strain is induced mechanically or by CAFs. By comparing purely mechanical and purely chemical migration to a 3D co-culture of CAFs and HCT-116 containing both chemical and mechanical cues, it is concluded that HCT-116 migration is dominated by mechanical signaling, while chemical cues are less influential.

Early-onset colorectal cancer (EOCRC) was characterized by strong aggressiveness and high malignancy. The aim of this study was to screen suitable biomarkers for patients with EOCRC. EOCRC from The Cancer Genome Atlas Program (TCGA) database and Gene Expression Mapping (GEO) database were used to screen biomarkers for prognosis and treatment guidance. Clinical samples were used to verify the expression situation of these candidate biomarkers. The results showed the immune-related gene nitric oxide synthase 2 (NOS2) was independently associated with the poor prognosis of EOCRC patients in both TGCA and GEO database. The Immune Dysfunction and Exclusion (TIDE) analysis showed that multiple immunotherapy signatures, such as TIDE, Exclusion, and CAF, were difference among EOCRC patients with different risk scores, and significantly correlated with the expression of NOS2. Sensitivity analysis of chemotherapy drugs showed that NOS2 was significantly correlated with several chemotherapy drugs, such as MG.132_1862, BMS.754807_2171, and GEN.317_1926. Clinical validation analysis showed that the expression of NOS2 and its related genes CXCL1 and CXCL2 were significantly decreased in EOCRC patients. The results suggested that NOS2 can be used as a potential biomarker for EOCRC, which can be used for prognosis and guidance of immunotherapy and chemotherapy.

Epigenetic clocks can quantify DNA methylation by measuring the methylation levels at specific sites in the genome, which correlate with biological age (BA). Accelerated aging, where BA exceeds chronologic age, has been studied in relation to cancer development, but its utility in cancer prevention remains unclear. Accelerated aging holds promise as a tool to explain the increase in early-onset colorectal cancer (EOCRC). We investigate the association of accelerated aging and the presence of preneoplastic polyps (PNP) in the colon, defined as tubular adenomas and sessile serrated adenomas. In this study of persons under age 50 undergoing colonoscopy, we used peripheral blood samples to determine BA and age acceleration metrics. Age acceleration was determined by interrogating DNA methylation at specific CpG sites across the genome, which has been shown to correlate with age. We then conducted logistic regression analyses to evaluate the association between age acceleration and PNPs. In total, 51 patient samples were evaluated. We found that that the odds of harboring a PNP are 16% higher with 1 year of accelerated aging, as measured by GrimAge. However, the strongest risk factor for PNPs remained male sex. This represents one of the first studies to explore accelerated aging and PNP in patients under the age of 50. A risk-stratified approach to EOCRC screening would minimize unnecessary colonoscopies and minimize healthcare burden while addressing the increase in EOCRC. Our findings suggest that BA calculations with peripheral blood collections could be an important component of such a risk model. Prevention Relevance: Understanding the association of accelerated aging and colorectal PNPs presents an opportunity to develop a risk-stratified approach to colorectal cancer screening in young persons.

In 2021, the USPSTF lowered the recommended age of colorectal cancer (CRC) screening initiation from 50 to 45 years. This study assessed clinician response to the updated guideline in a major health system.

This was a retrospective cohort study of average-risk, CRC screening-naïve adults aged 45-50 years with a primary care appointment between July 2018 and February 2023. The authors defined the pre-guideline change period as July 2018-February 2020 (pre-period) and the post-guideline change period as July 2021-February 2023 (post-period). Clinician ordering of any CRC screening type was assessed. Mixed effects Poisson regression was used to model the incidence rate ratio (IRR) of a patient receiving a screening order, including an interaction between age (45-49 years versus 50 years) and time period (pre- versus post-guideline change.) Variation in screening orders were also described by calendar quarter and clinician.

There were 28,114 patients in the pre-period and 22,509 in the post-period. Compared to patients aged 40-49 years in the pre-period, those in the post-period were more likely to have screening ordered (IRR=12.1; 95% CI=11.3-13.0). The screening ordering rate increased for patients aged 50 years from the pre- to the post-period (IRR=1.08; 95% CI=1.01, 1.16) and was slightly higher than that of patients aged 45-49 years in the post-period (IRR=1.08; 95% CI=1.02, 1.14). All clinicians increased their ordering rate for patients aged 45-49 years. Within 5 months of the guideline change, the ordering rate for patients aged 45-49 years and 50 years was nearly the same.

Rapidly following the guideline change, clinicians increased their screening ordering rate for patients aged 45-49 years, indicating almost complete uptake of the recommendation.

Despite a reduction of both incidence and mortality from CRC, recent studies have shown an increase in the incidence of early-onset CRC (EO-CRC). Data on this setting are limited. The aim of our study was to evaluate the clinical and molecular profiles of metastatic EO-CRC patients in order to identify differences compared to a late-onset CRC (LO-CRC) control group.

We retrospectively collected data from 1272 metastatic colorectal cancers from 5 different Italian Institutions. The main objective was to the evaluate clinical outcome for EO-CRC patients in comparison to patients included in the control group.

In the overall population, mOS was 34,7 in EO-CRC pts vs 43,0 months (mo) (p < 0,0001). In the RAS/BRAF mutated subgroup mOS in EO-CRC pts was 30,3 vs 34,0 mo (p = 0,0156). In RAS/BRAF wild-type EO-CRC mOS was 43,0 vs 50,0 mo (p = 0,0290). mPFS was 11,0 in EO-CRC pts vs 14,0 mo (p < 0,0001).

Findings indicate a general worse prognosis for patients with early-onset colorectal cancer compared to late-onset patients. Interestingly this seems to occur regardless of the molecular status. These observations might have a considerable impact on clinical practice and research.

Colorectal cancer (CRC) is linked to obesity, particularly visceral fat. A more accurate measure of visceral fat accumulation is offered by a body shape index (ABSI). Currently, the direct application of the ABSI to populations with varying ethnic backgrounds might be restricted. Moreover, there is less evidence about the correlation between ABSI and CRC among individuals from different ethnical backgrounds.

A total of 40,998 individuals who took part in the National Health and Nutrition Examination Survey (NHANES) spanning from 2003 to 2023 were subjected to analysis. Logistic regression was utilized to examine the associations between the ABSI and the risk of CRC. In addition, restricted cubic spline curves (RCS) were utilized, and subgroup analyses along with interaction tests were also carried out. The receiver operating characteristic curve (ROC) was employed to predict the risk of CRC relying on various anthropometric indicators.

After adjusting for covariates, ABSI demonstrated a positive association with the incidence of CRC (OR = 1.03 [95% CI: 1.01-1.05], p = 0.018). Individuals in the upper quartile of ABSI exhibited a greater prevalence of CRC than those in the lower quartile (OR = 1.88 [95% CI: 1.19-2.96], p = 0.006). RCS analysis indicated a nonlinear correlation between ABSI and CRC (P for nonlinear = 0.030). Subgroup analysis indicated a notable interaction between age and BMI subgroups (interaction p < 0.05), and ROC curves indicated that the ABSI was effective in predicting CRC risk (AUC = 0.658), demonstrating good sensitivity, particularly in individuals under 60 years of age.

A positive correlation exists between ABSI levels and the increased incidence of CRC among U.S. adults. This is especially true for people under 60 years of age (40-60 years), with a BMI below 25 kg/m2, and those with a BMI of 30 kg/m2 or beyond. ABSI can be used as a simple anthropometric predictor of CRC.

The epithelial and mesenchymal features of colorectal adenocarcinoma (CRAC) cell lines were compared in two-dimensional (2D) and three-dimensional (3D) cultures. In 2D cultures, the three CRAC cell lines exhibited epithelial characteristics with high E-cadherin and low vimentin levels, whereas two exhibited mesenchymal traits with opposite expression patterns. In 3D cultures using low-attachment plates, mesenchymal cells from 2D cultures showed reduced vimentin mRNA levels. Morphologically, the five CRAC cell lines appeared similarly shaped in 2D culture but formed different structures in 3D culture. Epithelial DLD-1 and mesenchymal COLO-320 cells produced large granular spheres, whereas epithelial HCT-15 cells formed small solid spheres. Tubular structures were observed in epithelial CACO-2 and mesenchymal SW480 spheres. Desmosome-like structures developed in epithelial CRAC cells, whereas entosis was observed in CACO-2, HCT-15, and SW480 cells. The Ki-67-positive proliferating cell count varied in 2D and 3D cultures of epithelial cells but remained high and unchanged in mesenchymal cells. These findings suggest that while CRAC cells display distinct epithelial and mesenchymal properties in 2D cultures, they form diverse 3D structures, irrespective of these traits.

Introduction  Performing colonoscopy in the elderly is associated with unique challenges, including higher rates of comorbidities, limited physiological reserve, and procedural complexities. This study aimed to evaluate the technical aspects, indications, and outcomes of colonoscopy in the elderly, with an emphasis on indication-based diagnostic yield. Methods  In this retrospective cohort study, we reviewed 35,000 consecutive colonoscopy procedures performed over a 12-year period on patients aged 50 years and older. Patients were categorized into three groups: very elderly (>80 years, n=3,434), elderly (65-80 years, n=13,783), and younger controls (50-64 years, n=17,959). Clinical and endoscopic findings were analyzed, with a focus on indication-specific outcomes. Results  The most frequent indications for colonoscopy in the very elderly and elderly groups were anemia and rectal bleeding. Both elderly groups exhibited higher rates of inpatient procedures (49.2% and 20.9% vs. 9.6%; P<0.0001), inadequate bowel preparation (18.5% and 13.5% vs. 9.1%; P<0.0001), and anesthesiologist involvement in sedation (6.0% and 3.9% vs. 2.1%; P=0.03) but required lower doses of propofol sedation (4.5% and 5.4% vs. 7.9%; P=0.026). Colorectal cancer (CRC), polyps, and diverticulosis detection increased linearly with age. Colonoscopies performed for anemia or rectal bleeding yielded higher CRC and polyp detection rates, whereas constipation was associated with the lowest diagnostic yield. Conclusion This study highlights the technical challenges associated with performing colonoscopy in elderly patients, identifies indications with the highest diagnostic yield, and underscores the necessity of tailored bowel preparation protocols and an indication-driven approach to optimize the clinical utility of colonoscopy in this population.

Objective: This study aimed to update the temporal trends for the incidences and case numbers of colorectal cancer (CRC) among individuals aged 45-49 in the US from 2001 to 2019.Methods: Patients were obtained from the National Program of Cancer Registries and Surveillance, Epidemiology and End Results Program (NPCR-SEER) database. Their age-adjusted incidence rates (AAIR) were calculated using the SEER*Stat software.Results: As high as 48.4% (125 604 cases) of the 259 700 early-onset CRC were diagnosed in individuals aged 45-49. Of these, 54.2% were males, and 40.7% were located in the rectum. Adenocarcinoma accounted for 93.9%, 96.5%, and 84.6% of proximal, distal colon, and rectal cancers, respectively. The incidences of proximal colon adenocarcinoma showed a significant increase, with an average annual percentage change (APC) of 0.7 from 2010 to 2019, while the case numbers remained stable from 2001 to 2019. In contrast, distal colon adenocarcinoma displayed increased incidences at an APC of 1.3 and an average increase of 17 cases annually over the study period. Rectal adenocarcinoma showed more rapid increases in incidence, with an average APC of 1.6 and an average increase of 27 cases per year. These rising incidences were predominately observed in non-Hispanic whites (NHWs). Conversely, non-Hispanic black (NHB) females showed decreased incidences of proximal and distal colon adenocarcinoma. Additionally, the incidences and case numbers for carcinoids significantly increased in the rectum but not in the colon.Conclusions: This study reveals distinct patterns of temporal trends in CRC incidences and case numbers among individuals aged 45-49. Further research is necessary to understand the underlying causes of the differences and to develop more effective preventive strategies to reduce the incidence of early-onset CRC.

Colorectal cancer (CRC) screening uptake remains suboptimal despite the importance and effectiveness of various testing options. The purpose of our study was to identify barriers and facilitators to CRC screening in a community-based sample in Salt Lake County, Utah to inform future efforts to develop effective interventions to increase CRC screening.

This study enrolled adults eligible for CRC screening at 6 community health events. Participants completed targeted questionnaires based on whether they had discussed screening with a provider and whether they had received screening. We identified participant-reported barriers to CRC screening using descriptive analysis. Univariate and multivariate analyses were used to identify participant characteristics associated with receipt of screening.

Of the 117 participants who completed the questionnaires, 43.6% were 50 to 60 years old, 36.8% identified as white, and 51.3% identified as non-Hispanic. The most common barrier to colonoscopy was the need for extensive bowel preparation (30.8%). For stool tests, common barriers included handling stool (20.5%) and not understanding how to do the test (20.5%). For virtual colonoscopy, barriers included the need for extensive bowel preparation (21.4%) and cost (21.4%). Most participants (67.5%) believed that they should know about all CRC screening options available, and their importance. The majority of participants (68.4%) preferred to learn about CRC screening from their doctor or healthcare provider. Younger age was associated with non-screening.

We observed that study participants faced procedural barriers to complete CRC screening and preferred to learn about CRC screening options through their providers. Younger age groups were less likely to receive screening within our study sample. Future, targeted interventions to increase CRC screening should focus on increasing the awareness of the importance of CRC screening and educating patients on the various screening options available and their benefits, especially as they pertain to less invasive tests and targeting younger individuals.

Previous studies have shown that colorectal cancer incidence is increasing among younger adults (aged <50 years) in multiple high-income western countries in contrast with stabilising or decreasing trends in incidence in older adults (aged ≥50 years). This study aimed to investigate contemporary colorectal cancer incidence trends in younger adults versus older adults.

Colorectal cancer incidence data, including year of diagnosis, sex, and 5-year age group for 50 countries and territories, were extracted from the WHO-International Agency for Research on Cancer Cancer Incidence in Five Continents Plus database. The Human Development Index 2022 was retrieved from the United Nations Development Programme and grouped into very high (>0·80), high (0·70-0·79), medium (0·55-0·69), and low (<0·55) categories. Age-standardised incidence rates (ASR) per 100 000 person-years of early-onset (diagnosed between ages 25 to 49 years) and late-onset (diagnosed between ages 50 to 74 years) colorectal cancer (ICD 10th revision, C18-20), diagnosed between 1943-2003 and 2015-17, were calculated using the direct method and Segi-Doll world standard population). The primary study objective was to examine contemporary colorectal cancer incidence trends in younger adults versus older adults using data until 2017 from 50 countries and territories. Temporal trends were visualised and quantified with joinpoint regression, stratified by age at diagnosis (25-49 years or 50-74 years). Average annual percentage changes (AAPC) were estimated.

In the most recent 5 years (2013-17 for all countries analysed, except for Japan [2011-15], Spain [2012-16], and Costa Rica [2012-16]), the incidence rate of early-onset colorectal cancer was highest in Australia (ASR 16·5 [95% CI 16·1-16·9]), the USA (Puerto Rico; 15·2 [14·2-16·2]), New Zealand (14·8 [14·0-15·6]), the USA (14·8 [14·7-14·9]), and South Korea (14·3 [14·0-14·5]) and lowest in Uganda (4·4 [3·6-5·2]) and India (3·5 [3·3-3·7]). The highest incidence rates among older adults were found in the Netherlands (168·4 [166·9-170·0]) and Denmark (158·3 [155·8-160·9]) and the lowest were in Uganda (45·9 [38·5-51·4]) and India (23·5 [22·8-24·3]). In terms of AAPC, in the most recent 10 years, incidence rates of early-onset colorectal cancer were stable in 23 countries, but increased in 27 countries with the greatest annual increases in New Zealand (AAPC 3·97% [95% CI 2·44-5·52]), Chile (3·96% [1·26-6·74]), Puerto Rico (3·81% [2·68-4·96]), and England (3·59% [3·12-4·06]). 14 of the 27 countries and territories showed either stable (Argentina, France, Ireland, Norway, and Puerto Rico) or decreasing (Australia, Canada, Germany, Israel, New Zealand, Slovenia, England, Scotland, and the USA) trends in older adults. For the 13 countries with increasing trends in both age groups, the average annual percentage increase in younger compared to older adults was higher in Chile, Japan, Sweden, the Netherlands, Croatia, and Finland; lower in Thailand, France (Martinique), Denmark, and Costa Rica; and similar in Türkiye, Ecuador, and Belarus. The rise in early-onset colorectal cancer was faster among men than women in Chile, Puerto Rico, Argentina, Ecuador, Thailand, Sweden, Israel, and Croatia, whereas faster increase among women compared to men was in England, Norway, Australia, Türkiye, Costa Rica, and Scotland.

Early-onset colorectal cancer incidence rates are rising in 27 of 50 countries and territories examined, with the rise either exclusive to early-onset disease or faster than the increase in older adults in 20 of the 27 countries. The findings underscore the need for intensified efforts to identify factors driving these trends and increase awareness to help facilitate early detection.

Intramural Research Program of the American Cancer Society, Cancer Grand Challenges, and National Institutes of Health.

The proportion of early onset colorectal cancer (EOCRC) is alarming in adults, including in African Americans (AA).

To investigate differences between EOCRC compared to late-onset colorectal cancer (LOCRC) among AA patients.

This retrospective study reviewed demographic, clinical presentations, colonoscopy, and pathology reports of patients at Howard University Hospital from 1959 to 2023. The study included 176 EOCRC cases (< 45 years) and 2034 LOCRC cases (> 45 years).

Both EOCRC and LOCRC groups were predominantly AA (> 80%) with slightly more females (53%) than males. The mean age was 38 years for EOCRC and 66 years for LOCRC cases. EOCRC cases increased as a proportion of total detected CRC cases since 2010 (over 13%) after several decades of just above 6%. Family history of CRC in first degree relatives was higher among EOCRC (15.5% vs.3.4% in LOCRC patients, p < 0.01). Symptoms at presentation were prevalent in both EOCRC (93.8%) and LOCRC (92.6%). EOCRC patients exhibited higher incidence of abdominal pain (23.3% vs. 17.2%, p = 0.05) and changes in bowel habits (24.4% vs. 14%, p < 0.01) compared to LOCRC patients. Other symptoms such as melena, hematochezia, and weight loss were less prevalent in EOCRC patients. Comorbidities like hypertension (HTN), diabetes mellitus (DM), and inflammatory bowel disease (IBD) were less frequent among EOCRC patients. EOCRC was primarily observed in the sigmoid and rectosigmoid regions (p = 0.02). Metastasis at index colonoscopy was more prevalent with EOCRC compared to LOCRC (p = 0.04), with a higher proportion of patients at stage 3 cancer (p < 0.05). Significant differences were noted in the timeline for undergoing surgery after the diagnosis of colorectal cancer, with EOCRC patients taking longer than LOCRC patients (p = 0.03).

Presentation of EOCRC over LOCRC increased proportionally in our cohort since 2010 and is associated with family history, and symptoms such as abdominal pain and change in bowel habits. Likely because of age at presentation, there are less comorbidities among EOCRC patients who predominantly present in the outpatient setting, and more likely diagnosed with advanced stage lesions that are predominantly sigmoid or rectosigmoid. These findings are similar to observations seen in the general population with EOCRC, albeit African American patients have commonly had earlier age presentation of CRC than White American patients.

For the early detection of colorectal cancer, it is important to identify the premalignant lesions to prevent cancer development. Non-invasive testing methods such as the faecal immunochemical test are well established for the screening and triage of patients with suspected colorectal cancer but are not routinely used for polyps. Additionally, the role of volatile organic compounds has been tested for cancer detection. The aim of this review was to determine the diagnostic accuracy of the faecal immunochemical test and volatile organic compounds in detecting colorectal polyps.

Original articles with diagnostic test accuracy measures for both the faecal immunochemical test and volatile organic compounds for advanced adenomas were included. Four databases including Medical Literature Analysis and Retrieval System Online (MEDLINE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, and Web of Science were searched. The quality assessment tool for diagnostic accuracy study was used to assess the risk of bias and applicability. Meta-analysis was performed using RStudio® and the combined faecal immunochemical test-volatile organic compounds sensitivity and specificity were computed.

Twenty-two faecal immunochemical tests and 12 volatile organic compound-related articles were included in the systematic review whilst 18 faecal immunochemical tests and eight volatile organic compound-related studies qualified for the meta-analysis. The estimated pooled sensitivity and specificity of the faecal immunochemical test to diagnose advanced adenoma(s) were 36% (95% c.i. 30 to 41) and 89% (95% c.i. 86 to 91) respectively, with an area under the curve of 0.65, whilst volatile organic compounds pooled sensitivity and specificity was 83% (95% c.i. 70 to 91) and 76% (95% c.i. 60 to 87) respectively, with an area under the curve of 0.84. The combined faecal immunochemical test-volatile organic compounds increased the sensitivity to 89% with a specificity of 67%.

Faecal immunochemical testing has a higher specificity but poor sensitivity for detecting advanced adenomas, while volatile organic compound analysis is more sensitive. The combination of both tests enhances the detection rate of advanced adenomas.

Recent increases in colorectal cancer (CRC) incidence and mortality under age 50 have led the US to recommend starting screening at age 45 years instead of 50. Several other countries are now also reconsidering the age to start CRC screening.

To aid decision makers in making an informed decision about lowering the starting age of CRC screening in their jurisdictions.

In this article, we present the clinical and modeling evidence for the optimal age to start CRC screening and provide a checklist of considerations for decisions on age to start CRC screening.

Two observational studies showed that detection of advanced neoplasia in those aged 45-49 years undergoing colonoscopy was at least as high as in those aged 50-54 years. One Taiwanese study reported a 22% reduction in CRC incidence and a 39% reduction in CRC mortality from FIT screening in those 40-49 years compared to those 50 years and older. Nine modeling studies concluded that lowering the age to start screening to age 45 was cost-effective. However, lowering the start age can have negative spill-off effects, such as increased wait times for diagnostic colonoscopy for symptomatic individuals and decreased screening participation. In an effort to support decision making and prevent negative spill-off, the National Colorectal Cancer Screening Network in Canada proposed a Worksheet to determine the resource impact of earlier screening initiation.

Lowering the age to start CRC screening to 45 years likely leads to a reduction in CRC incidence and mortality but requires additional healthcare resources. Policy makers can use the worksheet to assess the expected increase and assess the feasibility within their jurisdictions.

Background Signet ring cell carcinoma (SRCC) is a rare subtype of colorectal cancer with significant variations in clinical characteristics and poor prognosis. However, there is limited data available in Pakistan. Therefore, we analyzed to examine the incidence, clinicopathological features, treatments, and outcomes of SRCC in colorectal cancer cases in Pakistan. Methods This study includes 214 primary signet ring cell carcinoma cases in the colon and rectum. All relevant clinical information extracts on demographic details, laboratory results, radiological findings, endoscopy, pathologic diagnoses, surgical interventions, neoadjuvant and adjuvant therapies, and their corresponding outcomes were undertaken from the same online database of hospital and analyzed using SPSS (SPSS Inc., Chicago, IL, USA), Chi-square test, and independent sample Kruskal-Wallis H test. Results The prevalence of SRCC was higher in younger patients (<50 years), 184 (86%). SRCC was more common in advanced stages T3 and T4, with 210 (98%) cases and 106 cases (49.5%) belonging to stage N2. In 27 cases (12.6%), there was already distant metastasis. The most common site of recurrent disease in SRCC patients was the peritoneum in about 50 (51.5%) patients, followed by multi-site metastases involving the lung, liver, bones, and lymph nodes. Conclusion Signet ring cell colorectal cancer (SRCC) manifests in Pakistan at a younger age and is diagnosed at a more advanced stage, often accompanied by peritoneal metastasis with elevated levels of recurrence due to relatively low rates of screening and the absence of national cancer data and guidelines. It is imperative that these issues should be addressed in order to alleviate the burden of this disease in our population.

Treatment outcomes of locally advanced rectal cancer have improved significantly in recent decades. This retrospective study aimed to assess the efficacy of neoadjuvant chemoradiotherapy (nCRT) followed by surgery in patients with T4 rectal cancer and the different outcomes between T4a and T4b patients.

A total of 60 clinically T4 rectal cancer patients who underwent nCRT were included in the analysis. Patient characteristics, treatment regimens, down-staging rates, pathological response, and overall survival (OS) were evaluated.

Both T4a and T4b patients experienced down-staging following nCRT (36.6% and 6.2% respectively; p = 0.021). T4a patients exhibited a higher rate of pathological complete response (pCR) than T4b patients (13.3% in T4a vs. 0% in T4b; p = 0.122). After a median follow-up of 36 months, the OS and recurrence-free survival (RFS) of T4a patients were significantly higher compared to T4b patients (hazard ratio [HR] = 2.52, 95% confidence interval [CI] 1.05-6.05, p = 0.038 for OS; HR = 2.32, 95% CI 1.09-4.92, p = 0.025 for RFS).

This study provides valuable insights into the effectiveness of nCRT in T4 rectal cancer patients. Although down-staging was observed in both T4a and T4b subgroups, achieving a pCR remains a challenge, particularly in T4b patients. Further research is needed to optimize treatment strategies and enhance pCR rates in T4 rectal cancer patients to improve oncologic outcomes.

In Saudi Arabia, colorectal cancer (CRC) is the most common cancer in men and the third in women, posing a significant health burden. A comprehensive report of CRC incidence rates and trends in Saudi Arabia is lacking. This study aims to examine trends in CRC incidence among the Saudi population.

We used data from the Saudi Cancer Registry to examine CRC age-specific incidence rates (ASIR) and age-standardized incidence rates (ASR) between 1997 and 2017. Joinpoint regression analysis was used to determine the magnitude and direction of observed trends stratified by age, sex, and CRC stage at diagnosis. Trends were measured using the annual percentage change (APC) and the average annual percentage change (AAPC) in CRC incidence rates.

In total, 19,463 new CRC cases were identified during the study period. Since 1997, ASR for CRC has steadily increased in men and women overall, irrespective of disease stages. The ASIR increased across all age groups and was more pronounced in older patients. Women aged 40-49 had a higher increase in incidence than men (AAPC= 5.3 % vs.4.7 %). Males aged 70-79 had an AAPC of 10.2 %, twice that of females (AAPC= 4.9 %). A consistent rise in ASIR was observed across all CRC stages and age groups in males and females. In recent years, males under 50 had a higher APC for distant CRC than females, while females aged 50-74 experienced a steeper increase in distant CRC than males.

We report a marked increase in the incidence of CRC over time in Saudi Arabia, affecting men and women across all age groups and disease stages at diagnosis. Our findings underscore the need to identify underlying risk factors and to develop and implement effective prevention policies and strategies, including screening programs to facilitate early detection and treatment.

The incidence of young-onset colorectal cancer (YOCRC; defined as patients who are diagnosed with CRC before age 50 years) is rising rapidly, and CRC is predicted to be the leading cause of cancer death in this age group by 2030. Yet, there has been limited research into the experiences and needs of patients with YOCRC and their caregivers. The goal of this study was to better understand the experiences and needs of patients with YOCRC and their caregivers.

Semistructured focus groups were conducted with patients with YOCRC, caregivers of patients with YOCRC, and bereaved caregivers of patients with YOCRC. Focus group discussion guides addressed the experience and impact of diagnosis and treatment of YOCRC. Results were analyzed using a thematic analysis informed by framework analysis.

Twenty patients and caregivers participated in three focus groups (eight patients, seven caregivers, and five bereaved caregivers). Four primary themes were identified: (1) feeling overwhelmed by the health care system and desiring patient navigation; (2) feeling isolated and wanting opportunities for peer support; (3) life disruption because of difficulty juggling multiple roles and desiring psychosocial support; and (4) enthusiasm about participation in research and genetic testing.

This study identified and described the unique experiences and care needs of patients with YOCRC and their caregivers. The findings provide evidence that specialized models of care are needed. The results of this study informed the development of a center dedicated to the care of patients with YOCRC.

The incidence of Early-Onset Colorectal Cancer (EOCRC) is increasing. However, the prognosis of EOCRC compared to Late-Onset Colorectal Cancer (LOCRC), and the ideal age for initial colorectal cancer (CRC) screening are not clear. In this study, we identified the pathological differences between the groups and determined the optimal screening age for CRC patients. We included 10,172 patients diagnosed with CRC from January 2011 to December 2021 in this study. Survival differences were compared by plotting Kaplan-Meier survival curves and conducting landmark analysis. Additionally, the diagnostic age of CRC patients was analyzed using age cumulative curves. Compared to LOCRC patients, EOCRC patients had a higher proportion of deficient mismatch repair (dMMR) and more advanced TNM staging (P < 0.05). The five-year survival of EOCRC patients was significantly better than that of LOCRC patients (P < 0.05). Laparoscopic surgery improved the long-term survival of EOCRC patients. Proficient mismatch repair (pMMR) favored the long-term survival of EOCRC patients. The survival rate of EOCRC patients at TNM stages I and II was higher than that of LOCRC patients at the same stages (P < 0.05). The age cumulative curve showed a substantial increase in the number of CRC patients at 40 years. The long-term prognosis of EOCRC patients is better than that of LOCRC patients, especially among those with pMMR, stages I-II, and who undergo laparoscopic surgery. For people with a high risk of cancer, such as a family history of cancer and poor lifestyle habits, the starting age for CRC screening should be 40 years.

Colorectal cancer is among the most frequently diagnosed cancers with high mortality rates and poses a serious threat to human health. Genistein (Gen) has been found to have anti-colorectal cancer effects, however, the molecular mechanisms by which genistein elicits its effects on colorectal cancer (CRC) cells have not been fully elucidated. In this study, we investigated the oxidative state of colorectal cancer cells during the antitumor action of Genistein and whether it can exert its antitumor effects through ferroptosis. Current research on the oxidative state of Genistein indicates that it exhibits both antioxidant and pro-oxidant properties. Different drug concentrations were applied to colorectal cancer cells, after which cell viability and key markers of ferroptosis, including reactive oxygen species (ROS), malondialdehyde (MDA), and Fe2+, were measured. We found that genistein significantly reduced the viability of colorectal cancer cells, and the expression of ferroptosis markers increased in a concentration-dependent manner. Subsequently, we treated cells with the ferroptosis inhibitor fer-1 in combination with genistein and observed a partial reversal of ferroptosis markers. These findings suggest that genistein exerts its antitumor effect by promoting iron-dependent oxidative damage-induced ferroptosis. To further elucidate the mechanism underlying ferroptosis modulation, we examined the protein and mRNA expression levels of the classical key ferroptosis molecules SLC7A11 and GPX4. We found that the expression levels of these molecules decreased, with GPX4 exhibiting a greater decrease. Overexpression of GPX4 reversed the pro-ferroptotic effect of genistein, indicating that genistein promotes ferroptosis occurrence by downregulating GPX4 expression. When the drug was applied to colorectal cancer cells, the expression of the transcription factor FoxO3 increased. Treatment of cells with the FoxO3 inhibitor JY-2 in combination with other drugs resulted in antagonism of ferroptosis markers. These findings suggest that genistein induces ferroptosis in colorectal cancer cells through the FoxO3/SLC7A11/GPX4 signaling pathway, thereby inhibiting tumor growth.

Rates of early-onset (before 50 years of age) colorectal cancer (EOCRC) are increasing, with notable differences across racial and ethnic groups. Limited data are available on EOCRC-related mortality differences when disaggregating racial and ethnic groups.

To investigate racial and ethnic differences in EOCRC mortality, including disaggregation of Asian American populations separately, including Native Hawaiian or Other Pacific Islander populations and specific Asian American groups, and to quantify the contribution of clinical and sociodemographic factors accounting for these differences.

This population-based cohort study included California Cancer Registry data for individuals aged 18 to 49 years with EOCRC between January 1, 2000, to December 31, 2019. Median follow-up was 4.2 (IQR, 1.6-10.0) years. The data analysis was conducted between July 1, 2021, and September 30, 2024.

Race and ethnicity defined as Asian American (and 7 disaggregated subgroups), Hispanic, Native Hawaiian or Other Pacific Islander, non-Hispanic American Indian or Alaska Native, non-Hispanic Black, and non-Hispanic White.

Cox proportional hazards regression models were used to measure association between race and ethnicity and CRC mortality risk, yielding adjusted hazard ratios (AHRs) and 95% CIs. Associations of sociodemographic, health system, and clinical factors with differences in mortality by racial and ethnic minority group were assessed using sequential modeling.

There were 22 834 individuals diagnosed with EOCRC between 2000 and 2019 (12 215 [53.5%] male; median age, 44 [IQR, 39-47] years). Racial and ethnic identity included 3544 (15.5%) Asian American, 6889 (30.2%) Hispanic, 135 (0.6%) Native Hawaiian or Other Pacific Islander, 125 (0.5%) non-Hispanic American Indian or Alaska Native, 1668 (7.3%) non-Hispanic Black, and 10 473 (45.9%) non-Hispanic White individuals. Compared with non-Hispanic White individuals, higher EOCRC mortality was found for Native Hawaiian or Other Pacific Islander (AHR, 1.34; 95% CI, 1.01-1.76) and non-Hispanic Black (AHR, 1.18; 95% CI, 1.07-1.29) individuals. Disaggregation of Asian American ethnic groups revealed notable heterogeneity, but no single group had increased EOCRC mortality risk after full adjustment for covariates. For Hispanic individuals, there was higher EOCRC mortality (AHR, 1.15 [95% CI, 1.08-1.22]) with the base model (adjustment for age, sex, and tumor characteristics), but the association disappeared once neighborhood socioeconomic status was added to the base model (AHR, 1.00 [95% CI, 0.94-1.06]). Similarly, there was higher EOCRC mortality among Southeast Asian individuals with the base model (AHR, 1.17 [95% CI, 1.03-1.34], but that association disappeared with the addition of insurance status to the model (AHR, 1.10 [95% CI, 0.96-1.25]).

In this cohort study, racial and ethnic disparities in EOCRC mortality were evident, with the highest burden among Native Hawaiian or Other Pacific Islander and non-Hispanic Black individuals. These results provide evidence of the role of social determinants of health in explaining these differences.

Colorectal cancer is one of the most common malignancies worldwide. Improvements in screening and treatment have allowed for earlier detection and longer survival. However, treatments, which may involve surgery, radiotherapy and/or chemotherapy, often lead to patients developing both gastrointestinal and non-gastrointestinal symptoms that can persist long term. This systematic review aims to understand better the non-gastrointestinal symptoms that patients develop after colorectal cancer treatment and how these are identified and assessed through the use of questionnaires.

The review was conducted according to PRISMA guidelines. Scopus, PubMed, Web of Science, PsycINFO and Cochrane Library were searched. Eligible studies evaluated the non-gastrointestinal symptoms that patients had developed and continued to have at 12 months or longer after treatment. Studies that were performed on patients who were within 12 months of treatment, who had a recurrent or a secondary cancer, had stage 4 cancer/were palliative or that looked solely at gastro-intestinal symptoms were excluded. Articles were limited to studies on human subjects written in English published between February 2012 and July 2024.

The searches identified 3491 articles. Thirty-seven articles met the inclusion criteria, of which, 33 were quantitative, 2 were qualitative and 2 were mixed methods study designs. Nearly two-thirds (n = 22) were cross-sectional studies, whereas 14 were longitudinal. One study had both a cross-sectional and longitudinal component to it. Most studies were of medium to high quality based on the Newcastle Ottawa Scale (n = 23) and were conducted in 14 countries, the majority of which were performed in the Netherlands (n = 14). The majority of participants in the included studies (n = 30/37) were men. There were also three studies that were performed with only female participants and one study that was performed with male participants only. The age range of research participants across all the studies was 29 to 89 years. Forty-five different validated questionnaires containing 5-125 question items were used to collect information on the side effects and impact of colorectal cancer treatment. Completion rate for questionnaires varied from 30 to 100% (median 63.5%). These determined effects on quality of life, emotional/psychological distress, sexual and urinary dysfunction, neuropathy, fatigue and hip pain.

This systematic review highlighted a wide range of longer-term non-gastrointestinal symptoms that frequently adversely affect QoL following treatment. These studies included highlighting the importance of nutrition/diet, physical activity, spirituality and communication in managing these long-term side effects.