The number of early-onset colorectal cancer survivors (EOCRCs) is increasing. The primary aim of rehabilitation after battling cancer is to enable patients to return to work, as they constitute a significant contributor to societal productivity. A predictive model was developed to identify priority populations requiring intervention and refine responses to increase their capacity to return to work after undergoing treatment for EOCRC.

The baseline information was collected before patients were discharged at the end of their treatment course. The data of patients who returned to work were collected at 1 and 2 years after discharge. A predictive variable model was developed via binary logistic regression. The TRIPOD checklist was used.

At 1 year, 64.7% of the EOCRC survivors had returned to work. Male sex, education, return to work self efficacy, re-entry readiness and social support increased the possibility of returning to work; higher levels of self-perceived fatigue and lower levels of family care decreased the possibility of returning to work within the 1-year model. At 2 years, 72.8% of the EOCRC survivors had returned to work. In the 2-year model, education, self-transcendence, return to work self efficacy, re-entry readiness and occupational environment increased the possibility of returning to work; self-perceived fatigue and psychosocial adjustment decreased the possibility of returning to work.

The results of this study can guide early assessment and intervention for EOCRC survivors, to facilitate their return to work.

Our microbiome is established during infancy, a time important for later health and long-term effects. Proton pump inhibitors and antibiotics are regularly prescribed during pregnancy. Both drugs cause microbiome disturbance and have been associated with increased cancer risk in adults, but effects of these drugs on the growing foetus and infant remain understudied.

The aim of this study is to study the association between prenatal and early life proton pump inhibitor and antibiotics exposure and the risk of childhood cancer.

This study is a retrospective population-based cohort design, using registry data on all births (n = 722,372) in Sweden between 2006 and 2016, according to the STROBE checklist. For women who had multiple children in the timeframe of the study, only the first child during the time period was included in the cohort. Exposure was defined as either ≥ 1 proton pump inhibitor or antibiotics prescription during pregnancy, or during the first 2 years of life. Outcome was defined as cancer at any time during the follow-up or cancer after the age of 2 years for early life exposure. Multivariable Cox proportional hazard models were used to calculate hazard ratios.

In total, 1091 (0.2%) children were diagnosed with malignant cancer during the follow-up. Prenatal exposure to proton pump inhibitors and antibiotics were not associated with an increased risk of cancer. Regarding early life exposure, proton pump inhibitors were associated with an increased risk of cancer at age two or older (adjusted hazard ratio [aHR] 3.68, 95% confidence interval [CI] 2.24-6.06).

We did not find evidence that prenatal proton pump inhibitors and antibiotics were associated with overall childhood cancer. However, proton pump inhibitors during early life were associated with an increased risk of childhood cancer, but indication on drug use was not available and confounding by indication may be present.

Disrupted cellular polarity (DCP) is a hallmark of solid cancer, the malignant disease of epithelial tissues, which occupies ~90% of all human cancers. DCP has been identified to affect not only the cancer cell's aggressive behavior but also the migration and infiltration of immune cells, although the precise mechanism of DCP-affected tumor-immune cell interaction remains unclear. This review discusses immunosuppressive tumor microenvironments (TME) caused by DCP-driven tumor cell proliferation with DCP-impaired immune cell functions. We will revisit the fundamental roles of cell polarity (CP) proteins in sustaining mammary luminal homeostasis, epithelial transformation, and breast cancer progression. Then, the current data on CP involvement in immune cell activation, maturation, migration, and tumor infiltration are evaluated. The CP status on the immune effector cells and their targeted tumor cells are highlighted in tumor immune regulation, including the antigen presentation and the formation of immune synapses (IS). CP-regulated antigen presentation and delivery and the formation of IS between the immune cells, especially between the immune effectors and tumor cells, will be addressed. Alterations of CP on the tumor cells, infiltrated immune effector cells, or both are discussed with these aspects. We conclude that CP-mediated tumor aggressiveness coupled with DCP-impaired immune cell disability may decide the degree of immunosuppressive status and responsiveness to immune checkpoint blockade (ICB). Further elucidating the dynamics of CP- or DCP-mediated immune regulation in TME will provide more critical insights into tumor-immune cell dynamics, which is required to invent more effective approaches for cancer immunotherapy.

This study analyzed targeted sequencing data from 6530 tissue samples from patients with metastatic Chinese colorectal cancer (CRC) to identify low mutation frequency and subgroup-specific driver genes, using three algorithms for overall CRC as well as across different clinicopathological subgroups. We analyzed 425 cancer-related genes, identifying 101 potential driver genes, including 36 novel to CRC. Notably, some genes demonstrated subgroup specificity; for instance, ERBB4 was found as a male-specific driver gene and mutations of ERBB4 only influenced the prognosis of male patients with CRC. This sex disparity of ERBB4 was validated in an independent large-scale Memorial Sloan Kettering Cancer Center CRC cohort with 2444 samples. Furthermore, using network-based stratification based on protein-protein interaction, we classified the microsatellite stable (MSS) and unstable (MSI) CRCs into six and three major subtypes, respectively, each showing unique phenotypes and prognoses. In MSS CRC, cluster 5 (APCAMER1-KRAS) and cluster 2 (RNF43-BRAF-PIK3CA) were predominant, and cluster 5 showed a superior overall survival compared with cluster 2. This extensive heterogeneity in driver gene mutations underscores the complexity of CRC and suggests significant implications for treatment and prognostic assessments.

The risk of colorectal advanced adenomas (CAAs) and colorectal cancer (CRC) in siblings aged ≤ 50 of patients diagnosed with early-onset CAAs (E-CAAs), defined as having CAA at or below 50 years, is poorly understood. This study examined the risks of adenomas, CAA, and CRC in siblings aged ≤ 50 of patients diagnosed with E-CAA.

This case-control study was conducted at a tertiary hospital in Vietnam. The participants included 96 cases who were siblings aged ≤ 50 of patients diagnosed with E-CAA. Controls were randomly selected from consecutive patients aged ≤ 50 who did not have siblings diagnosed with E-CAA. Controls were matched to cases in a 2:1 ratio for age, sex, and smoking status.

The mean age was similar between cases (40.9 ± 6.0 years) and controls (41.1 ± 6.0 years). Except for indications for colonoscopy, there were no significant differences in the baseline demographics between the two groups. A heightened risk of CAA was documented in cases compared with controls (odds ratio [OR] 6.33; 95% confidence interval [CI] 1.43-43.8; P = 0.018). This increased risk was more pronounced in males (OR 13.7; 95% CI 1.23-262; P = 0.006). Cases had higher risks of colorectal adenomas (OR 2.43; 95% CI 1.27-4.67; P = 0.009) and colorectal neoplasia (OR 2.33; 95% CI 1.24-4.40; P = 0.011) than those in controls.

Siblings aged ≤ 50 of patients diagnosed with E-CAA have an increased risk of adenomas, CAA, and colorectal neoplasia. CRC screening should be initiated early in these high-risk individuals.

Colorectal cancer (CRC) is still one of the leading causes of cancer deaths worldwide. Even though there has been progress in cancer immunotherapy, the results of applying immune checkpoint inhibitors (ICIs) have been unsatisfactory, especially in microsatellite stable (MSS) CRC. Single-agent ICIs that target programmed cell death-1 (PD-1)/ PD-L1, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), T cell Ig- and mucin-domain-containing molecule-3 (TIM-3), and lymphocyte activation gene (LAG)-3 have emerged as having specific benefits. However, many primary and secondary resistance mechanisms are available in the tumor microenvironment (TME) that prevent it from happening. Combination strategies, such as the use of anti-PD-1 and anti-CTLA-4, can be effective in overcoming these resistance pathways, but toxicities remain a significant concern. Moreover, ICIs have been integrated with various treatment modalities, including chemotherapy, radiotherapy, antibiotics, virotherapy, polyadenosine diphosphate-ribose polymerase (PARP) inhibitors, and heat shock protein 90 (HSP90) inhibitors. The outcomes observed in both preclinical and clinical settings have been encouraging. Interestingly, manipulating gut microbiota via fecal microbiota transplantation (FMT) has been identified as a new strategy to increase the efficacy of immunotherapy in CRC patients. Therefore, integrating ICIs with other treatment approaches holds promise in enhancing the prognosis of CRC patients. This review focuses on the unmet need for new biomarkers to select patients for combination therapies and the ongoing work to overcome resistance and immune checkpoint blockade.

Colorectal cancer (CRC) is the third most common cancer worldwide, accounting for approximately 10% of all malignancies. Emerging trends of association with risk factors such as diverticulitis highlight the need for updated screening and follow-up protocols. We aimed to examine risk factors associated with the development of CRC within 12 months following an episode of acute diverticulitis, and identify areas to streamline follow-up.

We performed a retrospective multicentre study of adult patients admitted in 2022 with computed tomography (CT) confirmed acute diverticulitis across four large NHS Trusts in the UK. Patient demographics, comorbidities, clinical presentation, vital signs, laboratory results, details of in-patient stay, and follow-up investigations were collected and analysed. Our primary outcome was the incidence of CRC within 12 months of index presentation with acute diverticulitis. Analysed secondary outcomes were potential patient risk factors associated with a diagnosis of CRC and follow-up protocols. All statistical analysis was performed using R (version 4.4) and P-values of < 0.05 were considered statistically significant.

A total of 542 patients with acute diverticulitis over the study period were included. The median age of our cohort was 62 (51-73) years, and 204 (37.6%) were male. Ten (1.8%) patients were diagnosed with CRC within the 12-month period. Hinchey grade Ib was significantly associated with CRC (OR 4.51, P = 0.028). Colonoscopic follow-up requests were associated with age between 40 and 60 years, mild white cell count (WCC) elevation, and a hospital stay of 3-7 days. Male gender, age between 18 and 40 years, and elevated C-reactive protein (CRP) were all strongly associated with CRC but not statistically significant. Follow-up was inconsistent with 53.7% of the cohort having luminal investigations.

The incidence of CRC was in-keeping with published literature. Hinchey grade 1b was significantly associated with a subsequent CRC diagnosis. These findings emphasise the need for specialised radiological review of CT scans to detect underlying malignancy. Moreover, standardised follow-up protocols following an episode of acute diverticulitis are needed to avoid missing malignant lesions.

As the global population ages, and rates of modifiable risk factors for cancer change, cancer incidence and mortality continue to increase. While we understand many modifiable risk factors related to diet, nutrition, bodyweight, and physical activity in adulthood that influence cancer risk, how exposure during childhood, adolescence, and young adulthood impacts cancer risk is less clear. This is partly because the timeline from initial mutation to cancer development and diagnosis can span several decades. This long latency period creates methodological, ethical, and financial issues; as well as resource and feasibility challenges in the design, implementation, and data analysis of lifecourse studies. As such, the large majority of lifecourse studies are observational, often using recall data which has inherent bias issues. Concurrently, a new research era has begun, with mature birth cohort studies that are phenotyped/genotyped and can support studies on adult cancer risk. Several studies and consortia contain information spanning the lifecourse. These resources can support association, mechanistic and epigenetic investigations into the influences of multi-disciplinary (e.g. genetic, behavioural, environmental) factors, across the lifecourse and critical time periods. Ultimately, we will be able to produce high-quality evidence and identify how/when early life risk factors impact cancer development and survival.

The incidence of early-onset colorectal cancer (EoCRC), defined as CRC diagnosed at < 50 years of age, is increasing globally. However, only a few studies are reported from Japan, and the clinicopathological features of EoCRC in Japanese patients remain unknown.

We retrospectively investigated consecutive Japanese patients who were pathologically diagnosed with invasive CRC at our hospital from January 2015 to December 2021. Patients were categorized into those who were diagnosed with CRC at < 50 years (early-onset group) and ≥ 50 years (late-onset group) of age. We compared the clinicopathological findings between the two groups.

The analysis included 731 patients. EoCRC was diagnosed in 46 patients　(6.3% of all patients). Of them, 41.3% demonstrated a positive fecal immunochemical test (FIT) for CRC screening as a diagnostic opportunity, which was significantly higher than that in the late-onset group (p = 0.032). Rectal cancer was significantly more prevalent in the early-onset group compared to the late-onset group (45.7% vs. 26.4%, p < 001). No significant difference in the rate of clinical stage at presentation was found between the two groups. Furthermore, patients with positive FIT were more likely diagnosed at an earlier stage.

EoCRC among Japanese patients tends to occur on the rectum and is more frequently diagnosed with FIT screening compared to late-onset CRC. Patients with advanced stage were diagnosed by symptoms, indicating the usefulness of FIT screening in diagnosing EoCRC at an early stage.

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 therapeutic and prognostic outcomes for colorectal cancer (CRC) remain unsatisfactory. Among multiple reported bioactive functionalities of Glycyrrhiza uralensis Fisch. one vital recently reported activity is its therapeutic role against numerous cancers but limited information is available related to its underlying key mechanisms and therapeutically active ingredients, especially against CRC treatment.

The aim of current study aims is to reconnoiter G. uralensis pharmacological basis and primary molecular mode of action in treating CRC.

For examining the G. uralensis active ingredients and underlying mechanism investigation against CRC including, potential anti-CRC phytochemicals, targets, and related signaling pathways, HPLC and Network-pharmacology analysis techniques was employed, respectively. Whereas, for binding capabilities of active components to their targets, molecular-docking, molecular dynamic simulation technique employed and cell proliferation assays screened the best anti-CRC components, followed by biological function experiments on SW480 cells for verification. Finally, the SW480-xenograft model and subsequent related experiments further confirmed the effect of Liquiritin on CRC.

Seven compounds were identified from G. uralensis through HPLC. Network pharmacology and molecular docking results indicated that G. uralensis components exhibited significant anti-cancer effects. These effects were mediated through cancer and MAPK-related signaling pathways, targeting TP53, SRC, STAT3, and PIK3CA proteins. In-vitro experiments showed that liquiritin had better anti-CRC effects compared to other components as it significantly repressed the SW480 propagation, development of colony, relocation, and invasion. Additionally, liquiritin has been shown to significantly reduce tumor size in tumor-bearing mice by targeting p53 and inhibiting the p38 MAPK pathway.

In G. uralensis, main API is liquiritin that target CRC tumorigeneses via inhibition of p53 and p38 MAPK, thus can be used for CRC therapy. The findings provide a solid pharmacological basis and potential therapeutic targets for G. uralensis in the treatment of CRC.

Individuals with a known risk of colorectal cancer (CRC) are recommended regular surveillance colonoscopies. Alternative surveillance strategies incorporating fecal immunochemical tests (FIT) may improve colonoscopy resource utilization and be more appropriate for those with a lower risk of CRC, particularly younger adults. This study compared younger (< 50 years) and older (≥ 50 years) adults' preferences for different CRC surveillance strategies.

Eight hundred individuals enrolled in a colonoscopy-based surveillance program were invited to complete a survey assessing CRC surveillance preferences. Preferences for colonoscopy frequency and the acceptability of two alternative protocols were assessed: (1) providing FIT between colonoscopies, and (2) a FIT-only strategy where colonoscopy would only be required after a positive FIT result.

A total of 102 younger (median age 41.4 years, 67.6% female) and 187 older (median age 68.5 years, 49.2% female) adults completed the survey. Surveillance preferences did not significantly vary by age group; most respondents preferred colonoscopies more often than their current frequency (< 50 years: 54.1%; ≥ 50 years: 58.1%). Although most participants (< 50 years: 91.2%; ≥ 50 years: 93.0%) agreed that FIT is important to complete between surveillance colonoscopies, only a small proportion were comfortable with FIT-only surveillance replacing colonoscopies (< 50 years: 27.5%; ≥ 50 years: 37.4%). Fear of CRC was a significant predictor of preferences for more frequent surveillance incorporating FIT in younger, but not older, adults.

Many individuals with an elevated risk of CRC wanted more frequent surveillance, regardless of their age. Extending surveillance colonoscopy intervals using FIT may be a more acceptable method of reducing colonoscopy frequency rather than utilizing a FIT-only approach.

This study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN #12619001743156).

The incidence of early-onset bowel cancer (EOBC) is increasing in Australia and globally. However, the burden of EOBC among First Nations Australians is rarely determined. This study aimed to quantify the diagnosis and survival rates of EOBC among First Nations Peoples in Queensland, Australia.

CancerCostMod, a linked administrative dataset of patients diagnosed with cancer in Queensland from 1st July 2011 to 30th June 2015, was used. EOBC was defined as a diagnosis of bowel cancer (i.e., colon, rectosigmoid, or rectal cancer) at 18-49 years of age. A multivariable logistic regression analysis was employed to determine the association of Indigenous status and other factors with a diagnosis of EOBC. Five-year survival rates were used to estimate the survival rate.

Of 11,702 bowel cancer cases, 9.2% (95% CI: 8.7%-9.7%) were EOBC, with 19% among First Nations peoples and 9% among Non-First Nations. First Nations Australians had 2.6 times the odds of EOBC diagnosis (95% CI: 1.7-4.0) compared with Non-First Nations Australians. Overall, EOBC patients showed a significantly higher 5-year survival rate of 77% compared with 60% for late-onset bowel cancer patients. However, First Nations EOBC patients showed a lower 5-year survival rate (73%) than Non-First Nations EOBC patients (77%).

First Nations Australians have more than double the diagnosis rates and lower 5-year survival for EOBC compared to Non-First Nations. Whilst the recent lowering of the age eligibility for the National Bowel Cancer Screening Program is a beneficial strategy to address the increasing incidence of EOBC, special consideration should be given to addressing the higher diagnosis rates and lower survival among First Nations Australians. This study raises the potential for further lowering the age eligibility for First Nations Australians to ensure younger First Nations Australians can access screening for earlier detection, thereby improving their survival from bowel cancer.

Ultra-processed foods (UPFs) have become a widely consumed food category in modern diets. However, their impact on gut health is raising increasing concerns. This review investigates how UPFs impact the gut microbiome and gut barrier, emphasizing gut dysbiosis and increased gut permeability. UPFs, characterized by a high content of synthetic additives and emulsifiers, and low fiber content, are associated with a decrease in microbial diversity, lower levels of beneficial bacteria like Akkermansia muciniphila and Faecalibacterium prausnitzii, and an increase in pro-inflammatory microorganisms. These alterations in the microbial community contribute to persistent inflammation, which is associated with various chronic disorders including metabolic syndrome, irritable bowel syndrome, type 2 diabetes, and colorectal cancer. In addition, UPFs may alter the gut-brain axis, potentially affecting cognitive function and mental health. Dietary modifications incorporating fiber, fermented foods, and probiotics can help mitigate the effects of UPFs. Furthermore, the public needs stricter regulations for banning UPFs, along with well-defined food labels. Further studies are necessary to elucidate the mechanisms connecting UPFs to gut dysbiosis and systemic illnesses, thereby informing evidence-based dietary guidelines.

Colorectal cancer (CRC) ranks among the highest in incidence and mortality rates globally. A significant portion of Colorectal cancer cases and deaths can be attributed to modifiable risk factors, with smoking, alcohol use, and high body mass index (BMI) being the three most prominent. However, the impact of these risk factors on Colorectal cancer across regions, genders, and age groups remains insufficiently characterized.

Utilizing data from the Global Burden of Disease (GBD) study 2019, restrictive cubic splines (RCS) and quantile regression analyses are applied to explore the relationship between the Socio-Demographic Index (SDI) and ASMR or ASDR. Additionally, gender differences, changes across different SDI levels, and age group trends in smoking, alcohol use, and high BMI over the 30-year period are analyzed. The Bayesian age-period-cohort (BAPC) model is employed to predict mortality trends from 2020 to 2030, aiming to explore the epidemiological and sociodemographic transitions in the Colorectal cancer disease burden attributed to smoking, alcohol use, and high BMI.

In 2019, the number of colorectal cancer deaths globally attributable to risk factors as smoking, alcohol consumption, and obesity increased to 142,931, 52,495, and 85,882 cases respectively, collectively accounting for approximately one-third of all Colorectal cancer-related deaths. Notably, there is an upward trend in early-onset Colorectal cancer mortality associated with these factors.

To reduce the burden of Colorectal cancer, it is recommended to enhance health education, promote smoking cessation and alcohol moderation, and increase the coverage and participation in Colorectal cancer screening, which are crucial for lowering Colorectal cancer mortality rates. These findings are vital for the development of public health policies and intervention measures to reduce the global disease burden. They provide guidance for Colorectal cancer prevention across different regions, genders, and age groups worldwide.

Colorectal cancer (CRC) patients have been shown to possess an altered gut microbiome. Diet is a well-established modulator of the microbiome, and thus, dietary interventions might have a beneficial effect on CRC. An attenuating effect of the ketogenic diet (KD) on CRC cell growth has been previously observed, however the role of the gut microbiome in driving this effect remains unknown. Here, we describe a reduced colonic tumor burden upon KD consumption in a CRC mouse model with a humanized microbiome. Importantly, we demonstrate a causal relationship through microbiome transplantation into germ-free mice, whereby alterations in the gut microbiota were maintained in the absence of continued selective pressure from the KD. Specifically, we identify a shift toward bacterial species that produce stearic acid in ketogenic conditions, whereas consumers were depleted, resulting in elevated levels of free stearate in the gut lumen. This microbial product demonstrates tumor-suppressing properties by inducing apoptosis in cancer cells and decreasing colonic Th17 immune cell populations. Taken together, the beneficial effects of the KD are mediated through alterations in the gut microbiome, including, among others, increased stearic acid production, which in turn significantly reduces intestinal tumor growth.

While improved screening rates have contributed to an overall decrease in the incidence of colorectal cancer (CRC), the incidence of early-age-onset CRC (EAO CRC; age <50 years) has increased. Here, we characterize the genetic alterations and tumor microenvironment (TME) for EAO and later-age-onset (LAO) CRCs to identify relevant biological differences that might point to etiologic factors.

A cohort of EAO (n = 60) and LAO (n = 93) CRC patients were evaluated for mutations by using targeted DNA sequencing and for TME differences by using immunohistochemistry and immunofluorescence. The Cancer Genome Atlas (TCGA) PanCancer Atlas colorectal adenocarcinoma cohort was evaluated for transcriptional changes between EAO (n = 82) and LAO (n = 510) patients.

KRAS and BRAF mutations were less frequent in EAO CRCs. Gene-set enrichment analysis of TCGA data revealed the downregulation of immune-related pathways in EAO CRCs. Both age cohorts had similar numbers of CD8+ tumor-infiltrating lymphocytes (TILs), although LAO patients had more CD4+ TILs and Th1-polarized CD4s. While significant associations between immune subsets and versican (VCAN), versikine, and alpha-smooth muscle actin (αSMA) were found, none of these trends differed between age cohorts. EAO patients trended towards greater VCAN accumulation in adjacent normal tissue, lower rates of VCAN proteolysis, and decreased αSMA accumulation vs LAO patients.

Overall, established EAO cancers are similar to LAO cancers in mutational profile and key TME features. High VCAN and αSMA expression in adjacent normal colon indicates a presence of factors that are associated with increased intestinal subclinical inflammation. Future mechanistic studies will be conducted to better understand the importance of these findings and related processes should be prioritized as potential etiologic factors for EAO tumorigenesis.

Colorectal cancer (CRC) is a prevalent and lethal malignancy. This study examines differences in clinical and prognostic characteristics of CRC between patients under 50 years and those aged 50 and above, treated at a reference hospital in Southern Brazil.

A retrospective cohort study was conducted, analyzing data from the Cancer Hospital Registry in Porto Alegre, RS. Patients diagnosed with colon or rectal adenocarcinoma between January 2013 and December 2017 were included. Variables analyzed included family history, alcoholism, smoking status, clinical staging, tumor laterality, clinical presentation, CEA levels at diagnosis, adjuvant chemotherapy, and neutrophil-to-lymphocyte ratio.

The study cohort included 1,121 patients, with 85% aged 50 years or older, and 15% younger than 50 years. Significant differences were observed in smoking status and clinical presentation, with younger patients presenting with a higher prevalence of obstruction/subocclusion at diagnosis, which may reflect differences in clinical presentation due to delayed diagnosis.

Age and lifestyle factors, particularly smoking, significantly influenced the clinical presentation and management of colorectal cancer. These findings underscore the importance of targeted prevention strategies and personalized treatment approaches for younger CRC patients.

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.

The incidence of early-onset colorectal cancer (EO-CRC) is surging, and by 2030, one-third of all CRCs will occur before the commonly recommended screening age of 50 years. The time required for EO-CRC to reach the metastatic stage is unknown, yet this knowledge is critical to tailor early-diagnosis screening strategies. Here, we discuss how defining a key biological feature of EO-CRC may be central to protecting young adults from an alarming and probably unprecedented tumor epidemic.

Chemotherapy is one of the main therapeutic methods for tumor treatment. However, improving the accuracy of personalized medication for chemotherapy remains challenging. In this study, we developed a novel microfluidic chip that features herringbone protrusions and three-dimensional (3D) microcolumn holes created from microcolumn arrays. This design allows for precise control over the size and number of 3D tumor cell spheroids. As tumor cells aggregate into clusters within the chip, an integrated microfluidic mixer enhances liquid mixing and improves contact between the spheroids and the culture medium, promoting their growth. By combining this 3D spheroid approach with a concentration gradient mixer, we effectively conducted dynamic and high-throughput evaluations of anti-tumor drugs. The chip successfully identified varying sensitivities of tumor cells from different patients to these drugs, aligning with clinical observations from postoperative follow-ups. These features indicated that the tumor cell spheroid integrated microfluidic chip is effective for drug evaluation methodologies and holds promising implications for clinical applications.

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.

Very early-onset colorectal cancer (EOCRC) was defined as CRC diagnosed before the age of 35 proposed by the latest EOCRC management guideline. Until now, the disease burden of very EOCRC has never been reported. This study aimed to explore the burden of very EOCRC across the past three decades.

We extracted the data from Global Burden of Disease Study to analyze the disease burden of very EOCRC. Risk factors for the burden of deaths and disability-adjusted life years (DALYs) due to very EOCRC were also explored in this study. Additionally, decomposition analysis and frontier analysis were also conducted.

Despite regional and gender variations, the global very EOCRC incidence cases increased from 21,874 (95 % UI: 20,386-23,470) to 41,545 (95 % UI: 37,978-45,523). Besides, the deaths cases also increased from 11,445 (95 % UI: 10,545-12,374) to 15,486 (95 % UI: 14,289-16,803), and the DALYs cases increased from 718,136 (95 % UI: 659,858-778,283) to 961,460 (95 % UI: 886,807-1,042,734). Decomposition analysis revealed the epidemiological change contributed most to the incidence burden of very EOCRC. Countries or regions with Sociodemographic Index (SDI) between 0.4 and 0.8 had greater disease burden improvement potential through frontier analysis. Diet low in milk, diet low in calcium, alcohol use, and high body-mass index were the main contributors to deaths and DALYs.

The increase in CRC burden among populations younger than 35 years globally requires vigilance from policy makers, physicians, and young individuals themselves, especially those regions experiencing faster growth burden of very EOCRC.

Bisphenol A (BPA) is a typical environmental endocrine disruptor which have been broadly confirmed to be associated with malignant tumors, including colorectal cancer (CRC). Lipid metabolism reprogramming performed important biological effects in cancer progression. While the role of lipid metabolism in CRC progression upon BPA exposure remain elusive. Here, we found that BPA exposure enhanced de novo ceramide synthesis in vitro, along with upregulated ceramide synthase in high-BPA tumor tissue of CRC patients. Simultaneously, we demonstrated that BPA exposure exacerbated tumor biological behavior and epithelial mesenchymal transition (EMT), concurrent with elevated EMT expression of CRC tissue in high BPA group. Subsequently, the inhibition of ceramide synthase and pharmacological stimulation experiments revealed that ceramide accumulation activated EMT and exacerbated CRC progression, including Cer (d18:1/16:0) and Cer (d18:1/24:1). Collectively our findings elucidated the pathogenesis of ceramide accumulation escalating tumor progression under environmental BPA exposure, providing a strong basis for further investigation of dysregulated ceramide metabolism to boost tumor development and avoid metastatic relapse.

Tryptanthrin (TRYP) is an indole quinazoline alkaloid with a range of pharmaceutical activities, but the specific mechanism of TRYP against colorectal cancer (CRC) remains obscure. The purpose of this study was to evaluate the antitumor effects of TRYP on CRC models both in vitro and in vivo and further analyze its concrete mechanisms. The results of the in vitro experiment show that TRYP effectively inhibited the proliferation and migration of SW620 cells, arrested the cell cycle at the S phase, and induced cell apoptosis. Deeply, TRYP dramatically increased the expression of Bax and cleaved caspase 3 while decreasing the expression of Bcl-2. The results of transcriptome sequencing implied that the inhibitory effects of TRYP were closely related to the mitogen-activated protein kinase (MAPK) signaling pathway, and the results of western blotting verified that TRYP could decrease the expression of p-Erk and increase the expression of p-p38 and p-Jnk. Besides, our results identified that topoisomerase I (Topo I) and indole amine 2,3-dioxygenase 1 (IDO1) were the targets of TRYP. In vivo, the results showed that different TRYP doses significantly inhibited tumor growth in mice, induced different degrees of necrosis in tumor tissues, decreased the expression level of Ki67 protein, and increased the apoptotic signal in tumor tissues. The findings demonstrated the inhibitory effects of TRYP on CRC, and the mechanisms were tightly connected to inhibiting the activity of Topo I and IDO1 and regulating the expression of the MAPK signaling pathway. Especially, it was first identified that TRYP could directly inhibit Topo I to arrest SW620 at the S phase. Therefore, this work established a scientific basis for the development of TRYP.

This study aimed to analyze the trends of early-onset colorectal cancer (EOCRC) among individuals aged 15 to 49 in China from 1990 to 2021 and compare them with global patterns using data from the Global Burden of Disease (GBD) study. The analysis focused on age-standardized incidence rates (ASIR), prevalence rates (ASPR), mortality rates (ASMR), and disability-adjusted life years (DALYs). Joinpoint regression was used to determine the average annual percentage change (AAPC), and the ARIMA model was employed to forecast trends from 2022 to 2050. Results showed a significant increase in ASIR and ASPR in China, with a more rapid rise compared to global trends. ASMR and DALYs showed a decline, indicating improved survival rates. However, the increasing DALYs in China suggest a growing health impact. The ARIMA projections indicate a continued increase in EOCRC burden in China, highlighting the need for enhanced prevention and early detection strategies. This study underscores the necessity for intensified public health interventions to address the rising incidence of EOCRC in China.

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths globally. The risk of disease increases with age, as most CRC patients are over 50 years old. Due to the progressive aging of societies in high-income countries, the problem of CRC will increase. This makes the development of new early detection methods and the implementation of effective screening programs crucial. Key areas of focus include raising population awareness about the importance of screening, educating high-risk populations, and improving and developing early diagnostic methods. The primary goal of this review is to provide a concise overview of recent trends and progress in CRC secondary prevention based on available information from clinical trials.

We aimed to assess the significance of sex and age compared to other clinical-pathological parameters in colorectal cancer (CRC).

Our study included a retrospective approach to CRC patients who underwent surgery at the 'Pius Brinzeu' County Clinical Emergency Hospital in Timisoara (PBECCHT), Romania. The analyzed parameters were: patient age and sex, tumor location, histological type, differentiation grade (G), extent of tumor (pT), lymph-node status (pN), distant metastasis status (pM), and lymphovascular invasion (LVI). The population was divided into three groups based on age, with those under 49 years old, 50 to 69 years old, and elderly (>70).

The study's inclusion criteria were met by 1885 patients, with a male-to-female ratio of 1.39:1. There were significant differences between the sexes in the anatomical location of tumors (p < 0.0001). Younger patients were more likely to have deeply invasive tumors (p = 0.0096), LVI (p = 0.0332), lymph-node metastases (p = 0.0158), and metastatic disease (p = 0.0017).

Over the ten-year period reviewed, the frequency of CRC cases has progressively increased, with males being diagnosed more often. In terms of patient age, the young population exhibits clinical features of aggressive evolution. Patient sex did not influence the analyzed parameters, except for tumor location, where right colon tumors are slightly more common in females.

The incidence of early-onset colorectal cancer (EOCRC) has been rising at an alarming rate in the USA, and EOCRC disproportionately affects racial/ethnic minorities. Here, we construct comprehensive profiles of EOCRC DNA methylomes at base-pair resolution for a cohort of Hispanic and African American patients.

We show the epigenetic landscape of these EOCRC patients differs from that of late-onset colorectal cancer patients, and methylation canyons in EOCRC tumor tissue preferentially overlapped genes in cancer-related pathways. Furthermore, we identify epigenetic alterations in metabolic genes that are specific to our racial/ethnic minority EOCRC cohort but not Caucasian patients from TCGA. Top genes differentially methylated between these cohorts included the obesity-protective MFAP2 gene as well as cancer risk susceptibility genes APOL3 and RNASEL.

In this study, we provide to the scientific community high-resolution DNA methylomes for a cohort of EOCRC patients from underrepresented populations. Our exploratory findings in this cohort highlight epigenetic mechanisms underlying the pathogenesis of EOCRC and nominate novel biomarkers for EOCRC in underrepresented populations.

To provide estimates and trends for burdens of early-onset colorectal cancer (EOCRC) from 1990 to 2021 at the global, regional, and national levels, and to provide projections of EOCRC burden through 2030.

A trend analysis based on the Global Burden of Diseases 2021. The joinpoint regression model was used to analyze the temporal trends on EOCRC burden by calculating the corresponding average annual percent changes (AAPCs). A decomposition analysis was used to understand the drivers of the changes in EOCRC burden. The relationship between socio-demographic index (SDI) and disease burden was assessed by the concentration index of inequality. In addition, we constructed a Bayesian age-period-cohort model to predict the burden of EOCRC worldwide from 2022 to 2030.

Globally, the burden of EOCRC increased significantly between 1990 and 2021, with the incidence rising from 5.43/100000 to 6.13/100000 (AAPC = 0.39), and the prevalence increasing from 29.65/100000 to 38.86/100000 (AAPC = 0.87). Over the same period, the death rate decreased from 2.98/100000 to 2.30/100000 (AAPC = - 0.84), whereas the disability-adjusted life-year (DALY) decreased from 148.46/100000 to 115.42/100000 (AAPC = - 0.82). In 2021, East Asia and China had the highest burden of EOCRC regionally and nationally. Decomposition analysis indicated the increase in EOCRC burden was mainly driven by population growth. The concentration index revealed that high-SDI countries had a greater burden of EOCRC than low-SDI countries. The global incidence and prevalence of EOCRC will rise continuously from 2022 to 2030.

Between 1990 and 2021, the incidence and prevalence of EOCRC have escalated, whereas the death rate and DALY rate have declined. The burden varied with sex, SDI, and geographical locations. Given the rising trend of EOCRC burden, coordinated efforts are needed to reduce the burden posed by this malignancy.

Gastrointestinal (GI) cancers account for over a quarter of all cancer-related deaths in the United States; however, the latest trends in their prevalence remain unclear.

Data on GI cancers were obtained from the Global Burden of Disease Study 2021. Age-standardized incidence rates (ASIR) and age-standardized mortality rates (ASMR) were estimated across various states, sexes, ages, and risk factors, and annual percentage changes were calculated.

From 2000 to 2021, liver cancer exhibited the greatest increase in both the ASIR and the ASMR, followed by pancreatic cancer. In contrast, stomach cancer showed the greatest decline, followed by colorectal cancer, esophageal cancer, and biliary tract cancer. Most GI cancers predominantly affect men and tend toward a younger age of onset. Geographic disparities exist in the burden of GI cancers and their risk factors. For esophageal, stomach, and colorectal cancers, mortality rates linked to diet and smoking decreased, whereas alcohol-related mortality increased in several states, especially West Virginia. Hepatitis C remains the leading cause of liver cancer, with intravenous drug use as the primary risk factor. Non-alcoholic steatohepatitis (NASH) is the fastest-growing cause of liver cancer, followed by excessive alcohol use. Mortality rates for pancreatic cancer due to high body-mass index and high fasting plasma glucose have increased across states and age groups.

The epidemiological trends of GI cancers in the U.S. have shifted substantially. States need to implement targeted policies that address specific populations and risk factors for each cancer type.

Colon cancer is a significant health concern, and obesity is a well-established risk factor. However, previous studies have mainly focused on assessing body weight as a risk factor for colon cancer at a specific time point. This nationwide cohort study investigated the association between body weight changes, which can fluctuate throughout an individual's lifespan, and the incidence of colon cancer using the South Korean population database provided by the National Health Insurance Service (NHIS). Participants who underwent biennial health screenings between 2004 and 2006, and had follow-up health check-ups between 2014 and 2016, were included in this study. Body weight changes were categorized as follows: < 5%, decrease 5-20%, decrease > 20%, increase 5-20%, or > 20%. The primary outcome was the incidence of newly diagnosed colon cancer. Statistical analysis was used to examine the relationship between body weight changes and the incidence of colon cancer stratified according to age and sex. The Kaplan-Meier method estimated the cumulative incidence of colon cancer, and Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI), adjusting for confounding factors. The analysis included data from 10,332,397 individuals, with a mean (± SD) age of 45.5 ± 13.1 years, and 54.9% were male. In males with a body mass index (BMI) range of 18-30 kg/m2, both a weight gain of 5-20% (HR 1.07, P > z 0.01 [95% CI 1.02-1.13]) and weight gain > 20% (HR 1.27, P > z 0.03 [95% CI 1.03-1.56]) were associated with an increased risk for colon cancer. In addition, males < 40 years of age exhibited a higher risk for colon cancer with > 20% weight gain (HR 1.65, P > z < 0.001 [95% CI 1.18-2.30]). Whereas, females within the BMI range of 18-30 kg/m2 who exhibited > 20% weight loss demonstrated a reduced risk (HR 0.77, P > z 0.04 [95% CI 0.60-0.98]). Moreover, females ≥ 40 years of age, who experienced weight loss > 20%, exhibited a decreased risk for colon cancer (HR 0.76; P > 0.02 [95% CI 0.60-0.96]). This nationwide cohort study demonstrated a relationship between body weight changes and the incidence of colon cancer, with differences based on sex and age. In particular, avoiding weight gain is crucial for males < 40 years of age, whereas weight loss could be beneficial for females > 40 years of age in reducing the risk of colon cancer.