Early-onset Colorectal Cancer Research Articles

Obesity and overweight are associated with worse survival in early-onset colorectal cancer

BackgroundObesity and its associated lifestyle are known risk factors for early-onset colorectal cancer and are associated with poor postoperative and survival outcomes in older patients. We aimed to investigate the impact of obesity on the outcomes of early-onset colorectal cancers. MethodsRetrospective review of all patients undergoing primary resection of colon or rectal adenocarcinoma at our institution between 2015–2022. Patients who had palliative resections, resections performed at another institution, appendiceal tumors, and were underweight were excluded. The primary endpoint was survival according to the patient's body mass index: normal weight (18–24.9 kg/m2), overweight (25–29.9 kg/m2), and obesity (≥30 kg/m2). Patient and tumor characteristics and survival were compared between the three groups. ResultsA total of 279 patients aged <50 years with colorectal cancer were treated at our hospital; 120 were excluded from the analysis for the following reasons: main treatment or primary resection performed at another hospital (n = 97), no resection/palliative resection (n = 23), or body mass index <18 kg/m2 (n = 2). Of these, 157 patients were included in the analysis; 61 (38.9%) were overweight and 45 (28.7%) had obesity. Except for a higher frequency of hypertension in the overweight (P = .062) and obese (P = .001) groups, no differences in patient or tumor characteristics were observed. Mean overall survival was 89 months with normal weight, 92 months with overweight, and 65 months with obesity (P = .032). Mean cancer-specific survival was 95 months with normal weight, 94 months with overweight, and 68 months with obesity (P = .018). No statistically significant difference in disease-free survival (75 vs 70 vs 59 months, P = .844) was seen. ConclusionIndividuals with early-onset colorectal cancer who are overweight or obese present with similar tumor characteristics and postoperative morbidity to patients with normal weight. However, obesity may have a detrimental impact on their survival. Addressing obesity as a modifiable risk factor might improve early-onset colorectal cancer prognosis.

Geographical Variations in Early Onset Colorectal Cancer in the United States between 2001 and 2020.

Colorectal cancer remains the second leading cause of cancer-related death in the US. As early-onset colorectal cancer (EO-CRC) becomes more prevalent in the US, research attention has shifted towards identifying at-risk populations. Previous studies have highlighted the rising rate of early-onset adenocarcinoma (ADC) and neuroendocrine tumors (NET) in the US. However, data on geographical variations of EO-CRC are scarce. Hence, our study aims to analyze time trends in EO-CRC incidence rates across various US regions and to assess these trends by sex and histopathological subtypes (ADC and NET). We analyze data spanning from 2001 to 2020 from the United States Cancer Statistics (USCS) database, covering nearly 98% of the US population. Using SEER*Stat software version (8.4.2, NCI), we calculated EO-CRC incidence rates among adults aged 20-54 years, adjusting for the age standard 2000 US population. The rates were categorized by sex and US geographical regions into west, midwest, northeast, and south. Time trends, reported as annual percentage change (APC) and average APC (AAPC), were generated via Joinpoint Regression software (v.5.0.2, NCI) utilizing the weighted Bayesian Information Criteria "BIC" method to generate the best-fit trends with a two-sided p-value cutoff at 0.05. The rates were also stratified by histopathology into ADC and NET. Between 2001 and 2020, a total of 514,875 individuals were diagnosed with early-onset CRC in the US, with 54.78% being men. Incidence rates and trends varied across geographical regions. In the western region (comprising 106,685 patients, 54.85% men), incidence rates significantly increased in both women (AAPC = 1.37, p < 0.001) and men (AAPC = 1.34, p < 0.001). Similarly, in the midwestern region (with 110,380 patients, 55.46% men), there were significant increases in incidence rates among women (AAPC = 1.06, p < 0.001) and men (AAPC = 1.35, p < 0.001). The northeastern region (with 94,758 patients, 54.53% men) also witnessed significant increases in incidence rates for both women (AAPC = 0.71, p < 0.001) and men (AAPC = 0.84, p < 0.001). In contrast, the southern region (with 203,052 patients, 54.48% men) experienced slower increases in incidence rates among both women and men (AAPC = 0.25, p < 0.05 in women; AAPC = 0.66, p < 0.05 in men). When stratified by histopathology, incidence rates for adenocarcinomas (ADC) increased in all regions, most notably in the west (AAPC = 1.45, p < 0.05), and least in the south (AAPC = 0.46, p < 0.05). Conversely, for neuroendocrine tumors (NET), while incidence rates increased similarly across all regions, the pace was notably faster compared to ADC, particularly in the west (AAPC = 3.26, p < 0.05) and slower in the south (AAPC = 2.24, p < 0.05) Discussion: Our analysis of nationwide US data spanning two decades and encompassing over half a million early-onset CRC patients, representing nearly 98% of the US population, highlights significant temporal variation in incidence rates across various geographical regions. The most substantial increases in incidence rates were observed in the west, while the least pronounced changes were noted in the south, affecting both men and women. These trends persisted across the main CRC histopathological subtypes, with NET exhibiting a notably swifter pace of increase compared with ADC. These findings hold important implications for public health strategies and underscore the need for targeted interventions to address the rising burden of early-onset CRC across different regions in the US.

Early-onset colorectal cancer: the importance of timely screening

Early-onset colorectal cancer: the importance of timely screening

Determinants of early-onset colorectal cancer: a multicenter case-control study in Iran.

We aimed to study the risk factors of early-onset colorectal cancer (CRC) incidence in the Iranian population. Early onset CRC in Iran is a relevant health issue that deserves further epidemiological efforts to be defined and controlled as far as possible. Early age screening of low-tract of the intestine would be particularly useful in families of colorectal cancer patients. We analyzed data from a multicenter hospital-based case-control study in Iran (The Iranian Study of Opium and Cancer). Sociodemographic and lifestyle information was collected using validated questionnaires. Multivariate logistic regressions estimated the odds ratios (OR) and 95% confidence intervals (CIs) for the association of early-onset CRC in individuals under the age of 50 and potential risk factors, including physical activity, socioeconomic status, body shape at age 15, dietary factors, vitamin D, cigarettes and waterpipe smoking, opium use and family history of CRC. Additionally, a subgroup analysis was conducted for individuals with a very young age of CRC onset (i.e. <35 years). We analyzed data of 189 developed CRC below age 50 (99 colon and 90 rectum), and 66 patients under the age 35 (13 colon and 21 rectum). Early CRC was inversely associated with vegetables (OR, 0.59; 95% CI, 0.38-0.92 for 422-576 g/day) and vitamin D (OR, 0.49; 95% CI, 0.26-0.94), and positively associated with red meat intake (OR, 1.80; 1.15-2.83 per 25.65 g/day). Vegetables (OR, 0.51; 95% CI, 0.27-0.98 for 576 g/day), red meat (OR, 2.05; 95% CI, 1.11-3.79 for 25.65 g/day), vitamin D (OR, 0.29; 95% CI, 0.10-0.86) and opium use (OR, 2.61; 95% CI, 1.01-6.74) were associated with early rectum cancer. Results were heterogeneous by cancer site for high fruit and vegetables intakes and cigarette smoking. Family history was associated with CRC (OR, 3.16; 95% CI, 1.29-10.9) and rectum cancer (OR, 3.22; 95% CI, 1.24-14.4) in subjects younger than 35, and, to a lesser extent, with CRC and rectum cancer before age 50. Early-onset CRC was related to the intake of vegetables, vitamin D and red meat in Iran. Early-onset rectum cancer was associated with regular opium use. Family history was associated with early CRC and early rectum cancer, particularly below the age of 35.

Genomic landscape of diploid and aneuploid microsatellite stable early onset colorectal cancer

Although colorectal cancer (CRC) remains the second leading cause of cancer-related death in the United States, the overall incidence and mortality from the disease have declined in recent decades. In contrast, there has been a steady increase in the incidence of CRC in individuals under 50 years of age. Hereditary syndromes contribute disproportionately to early onset CRC (EOCRC). These include microsatellite instability high (MSI+) tumors arising in patients with Lynch Syndrome. However, most EOCRCs are not associated with familial syndromes or MSI+ genotypes. Comprehensive genomic profiling has provided the basis of improved more personalized treatments for older CRC patients. However, less is known about the basis of sporadic EOCRC. To define the genomic landscape of EOCRC we used DNA content flow sorting to isolate diploid and aneuploid tumor fractions from 21 non-hereditary cases. We then generated whole exome mutational profiles for each case and whole genome copy number, telomere length, and EGFR immunohistochemistry (IHC) analyses on subsets of samples. These results discriminate the molecular features of diploid and aneuploid EOCRC and provide a basis for larger population-based studies and the development of effective strategies to monitor and treat this emerging disease.

Comparative characteristics of early-onset vs. late-onset advanced colorectal cancer: a nationwide study in China

BackgroundThe incidence of early-onset colorectal cancer (EOCRC, diagnosed in patients under the age of 50 years) has been increasing around the world. Here, we aimed to systematically identify distinctive features of EOCRC.MethodsFrom 2020 to 2021, we conducted a nationwide survey in 19 hospitals, collecting data on advanced CRC patients’ demographics, clinical features, disease knowledge, medical experiences, expenditures, and health-related quality of life (HRQOL). We compared these features between EOCRC and late-onset colorectal cancer (LOCRC, ≥ 50 years old) groups and analyzed the association between EOCRC and HRQOL using multivariate linear regression.FindingsIn total, 991 patients with EOCRC and 3581 patients with LOCRC were included. Compared to the LOCRC group, the EOCRC group had higher levels of education, were more informed about the risk factors for CRC, were more likely to have widespread metastases throughout the body, were more inclined to undergo gene testing, and were more likely to opt for targeted therapy, radiotherapy, and chemotherapy. However, HRQOL in the EOCRC group was similar to that of the LOCRC group, and no significant association was observed between EOCRC and HRQOL (beta: -0.753, P value: 0.307).InterpretationIn Chinese patients, EOCRC patients had more aggressive features. Despite undergoing more intensified treatments and gene testing, they had similar HRQOL compared with LOCRC. These findings advocate for a more tailored approach to treatment, especially for young CRC patients with advanced TNM stages and metastasis.

Colorectal cancer screening: A review of current knowledge and progress in research.

Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide, being the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths globally. Despite the progress in screening, early diagnosis, and treatment, approximately 20%-25% of CRC patients still present with metastatic disease at the time of their initial diagnosis. Furthermore, the burden of disease is still expected to increase, especially in individuals younger than 50 years old, among whom early-onset CRC incidence has been increasing. Screening and early detection are pivotal to improve CRC-related outcomes. It is well established that CRC screening not only reduces incidence, but also decreases deaths from CRC. Diverse screening strategies have proven effective in decreasing both CRC incidence and mortality, though variations in efficacy have been reported across the literature. However, uncertainties persist regarding the optimal screening method, age intervals and periodicity. Moreover, adherence to CRC screening remains globally low. In recent years, emerging technologies, notably artificial intelligence, and non-invasive biomarkers, have been developed to overcome these barriers. However, controversy exists over the actual impact of some of the new discoveries on CRC-related outcomes and how to effectively integrate them into daily practice. In this review, we aim to cover the current evidence surrounding CRC screening. We will further critically assess novel approaches under investigation, in an effort to differentiate promising innovations from mere novelties.

Do treatment patterns differ in those with early-onset colorectal cancer?

ABSTRACT Background The incidence of early-onset colorectal cancer (EOCRC) is increasing. International guidelines state that treatment should not differ from that of older patients. Several studies have shown that patients under 50 years are receiving more aggressive treatment, without any survival benefit. We aim to determine if treatment for stages 2 and 3 EOCRC differs from those of late-onset colorectal cancer (LOCRC) patients. Methods This was a retrospective, population-based, cohort study of the treatment patterns of patients diagnosed with colorectal cancer in Canterbury, New Zealand, from 2010 to 2021 age <50 years, compared to those aged 60–74 years. Results A total of 3263 patients were diagnosed with CRC between 2010 and 2021. Following exclusions, we identified 130 EOCRC and 668 LOCRC patients. Stage 2 EOCRC patients are more likely to be offered adjuvant chemotherapy (p = <0.001). Furthermore, EOCRC patients with either stage 2 or 3 disease are more likely to receive multi-agent therapy (p = <0.01), without any associated increase in survival. Conclusion EOCRC patients are given more adjuvant chemotherapy, without a corresponding improvement in outcomes, highlighting a potential for increased treatment-related harms, particularly in stage 2 disease. Clinicians should be mindful of these biases when treating young cancer patients and need to carefully consider treatment-related harms.

The incidence of early onset colorectal cancer in Aotearoa New Zealand: 2000–2020

BackgroundThe incidence of early-onset colorectal cancer (EOCRC), diagnosed before age 50, has been rising in many countries in the past few decades. This study aims to evaluate this trend in Aotearoa New Zealand and assess its impact on Māori.MethodsCrude incidence and age-standardized incidence of colorectal cancer (CRC) was analyzed from all new cases from the Aotearoa New Zealand national cancer registry for the period 2000–2020. Trends were estimated by sex, ethnicity, age group and location of cancer and projections made to 2040.ResultsBetween 2000 and 2020, there were a total of 56,761 cases of CRC diagnosed in Aotearoa New Zealand, 3,702 of these being EOCRC, with age-standardized incidence decreasing significantly (P = 8.2 × 10− 80) from 61.0 to 47.3 cases per 100,000. EOCRC incidence increased on average by 26% per decade (incidence rate ratio (IRR) 1.26, p = < 0.0001) at all sites (proximal colon, distal colon and rectum), while the incidence in those aged 50–79 years decreased on average by 18% per decade (IRR 0.82, p = < 0.0005), again across all sites. There was no significant average change in CRC incidence in those over 80 years. In Māori, there was no significant change in age-standardized incidence. There was however a significant increase in crude incidence rates (IRR 1.28, p = < 0.0005) driven by significant increases in EOCRC (IRR1.36, p = < 0.0005). By 2040, we predict the incidence of EOCRC will have risen from 8.00 to 14.9 per 100,000 (6.33 to 10.00 per 100,000 in Māori). However, due to the aging population an estimated 43.0% of all CRC cases will be diagnosed in those over 80 years of age (45.9% over 70 years of age in Māori).ConclusionThe age-standardized incidence of CRC from 2000 to 2020 decreased in Aotearoa New Zealand, but not for Māori. The incidence of EOCRC over the same period continues to rise, and at a faster rate in Māori. However, with the ageing of the population in Aotearoa New Zealand, and for Māori, CRC in the elderly will continue to dominate case numbers.

Identification of differentially expressed genes and splicing events in early-onset colorectal cancer.

The incidence of colorectal cancer (CRC) has been steadily increasing in younger individuals over the past several decades for reasons that are incompletely defined. Identifying differences in gene expression profiles, or transcriptomes, in early-onset colorectal cancer (EOCRC, < 50 years old) patients versus later-onset colorectal cancer (LOCRC, > 50 years old) patients is one approach to understanding molecular and genetic features that distinguish EOCRC. We performed RNA-sequencing (RNA-seq) to characterize the transcriptomes of patient-matched tumors and adjacent, uninvolved (normal) colonic segments from EOCRC (n=21) and LOCRC (n=22) patients. The EOCRC and LOCRC cohorts were matched for demographic and clinical characteristics. We used The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) database for validation. We used a series of computational and bioinformatic tools to identify EOCRC-specific differentially expressed genes, molecular pathways, predicted cell populations, differential gene splicing events, and predicted neoantigens. We identified an eight-gene signature in EOCRC comprised of ALDOB, FBXL16, IL1RN, MSLN, RAC3, SLC38A11, WBSCR27 and WNT11, from which we developed a score predictive of overall CRC patient survival. On the entire set of genes identified in normal tissues and tumors, cell type deconvolution analysis predicted a differential abundance of immune and non-immune populations in EOCRC versus LOCRC. Gene set enrichment analysis identified increased expression of splicing machinery in EOCRC. We further found differences in alternative splicing (AS) events, including one within the long non-coding RNA, HOTAIRM1. Additional analysis of AS found seven events specific to EOCRC that encode potential neoantigens. Our transcriptome analyses identified genetic and molecular features specific to EOCRC which may inform future screening, development of prognostic indicators, and novel drug targets.

Construction and validation of a nomogram for predicting overall survival of patients with stage III/IV early-onset colorectal cancer.

This study aimed to identify prognostic factors and develop a nomogram for predicting overall survival (OS) in stage III/IV early-onset colorectal cancer (EO-CRC). Stage III/IV EO-CRC patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. The datasets were randomly divided (2:1) into training and validation sets. A nomogram predicting OS was developed based on the prognostic factors identified by Cox regression analysis in the training cohort. Moreover, the predictive performance of the nomogram was assessed using the receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Subsequently, the internal validation was performed using the validation cohort. Finally, a risk stratification system was established based on the constructed nomogram. Of the 10,387 patients diagnosed with stage III/IV EO-CRC between 2010 and 2015 in the SEER database, 8,130 patients were included. In the training cohort (n=3,071), sex, marital status, race/ethnicity, primary site, histologic subtypes, grade, T stage, and N stage were identified as independent prognostic variables for OS. The 1-, 3-, and 5-year area under the curve (AUC) values of the nomogram were robust in both the training (0.751, 0.739, and 0.723) and validation cohorts (0.748, 0.733, and 0.720). ROC, calibration plots, and DCA indicated good predictive performance of the nomogram in both the training and validation sets. Furthermore, patients were categorized into low-, middle-, and high-risk groups based on the nomogram risk score. Kaplan-Meier curve showed significant survival differences between the three groups. We developed a prognostic nomogram and risk stratification system for stage III/IV EO-CRC, which may facilitate clinical decision-making and individual prognosis prediction.

Symptom Burden and Time from Symptom Onset to Cancer Diagnosis in Patients with Early-Onset Colorectal Cancer: A Multicenter Retrospective Analysis.

Background: The incidence of colorectal cancer (CRC) is decreasing in individuals >50 years due to organised screening but has increased for younger individuals. We characterized symptoms and their timing before diagnosis in young individuals. Methods: We identified all patients diagnosed with CRC between 1990-2017 in British Columbia, Canada. Individuals <50 years (n = 2544, EoCRC) and a matched cohort >50 (n = 2570, LoCRC) underwent chart review to identify CRC related symptoms at diagnosis and determine time from symptom onset to diagnosis. Results: Across all stages of CRC, EoCRC presented with significantly more symptoms than LoCRC (Stage 1 mean ± SD: 1.3 ± 0.9 vs. 0.7 ± 0.9, p = 0.0008; Stage 4: 3.3 ± 1.5 vs. 2.3 ± 1.7, p < 0.0001). Greater symptom burden at diagnosis was associated with worse survival in both EoCRC (p < 0.0001) and LoCRC (p < 0.0001). When controlling for cancer stage, both age (HR 0.87, 95% CI 0.8-1.0, p = 0.008) and increasing symptom number were independently associated with worse survival in multivariate models. Conclusions: Patients with EoCRC present with a greater number of symptoms of longer duration than LoCRC; however, time from patient reported symptom onset was not associated with worse outcomes.

Number of Older Biological Siblings and Early-Onset Colorectal Cancer Risk

Colorectal cancer (CRC) is the third most common cancer in the United States.1 Although CRC incidence has declined in individuals >50 years, incidence is rising in adults <50 years (early onset).1 By 2027, CRC is projected to become the leading cause of cancer mortality in US adults <50 years.2 To combat the rising incidence of early onset CRC (EOCRC), national guidelines recently lowered the screening age from 50 to 45 years for average-risk individuals.3 Understanding the risk profile of EOCRC can help combat the rising burden in young adults, especially in those ineligible for screening.

Abstract LB134: Mutational signatures in colorectal cancer from 11 countries reveal new insights in early-onset colorectal cancer

Abstract Background: Colorectal cancers (CRC) have an important impact on both incidence and mortality worldwide, with varying rates in different parts of the world. Despite an overall decrease in incidence in the past years, an alarming increase in early onset colorectal cancer (CRC in patients under 50 years of age) rates has been observed. As part of the Cancer Research UK Grand Challenge Mutographs project, we aim to better understand the underlying mutagenic causes contributing to the differences in CRC incidence rates through mutational signatures. Methods: We collected epidemiological data and performed whole genome sequencing and mutational signature analysis on 981 CRC tumor samples from 11 countries with varying incidence rates, including intermediate incidence regions (Iran, Colombia, Thailand, and Brazil) and higher incidence regions (Argentina, Russia, Canada, Poland, Czechia, Serbia, and Japan). Results: The average mutational profiles were similar across the countries. Mutational signatures associated with DNA repair deficiencies, including POLE and POLD1 associated signatures (SBS10a/b/c/d and SBS28), MUTYH (SBS36), NTHL1 (SBS30), homologous recombination deficiency (SBS3), and a plethora of microsatellite instability (MSI) signatures, were found in 177 cancers (18% of all samples) and at comparable levels across all countries. Multiple signatures with known etiologies were found in 802 DNA repair proficient colorectal cancers including clock-like (SBS1 and SBS5), reactive oxygen species (SBS18), APOBEC (SBS2 and SBS13), and the microbiome-product colibactin (SBS88) signatures. The colibactin signature SBS88 was observed in 14% of samples overall, being more prevalent in distal and rectum tumors. SBS88 was significantly enriched in younger patients (33% &amp;lt;40y, 23% 40-49y, 20% 50-59y,10% 60-69y, 10% ≥70y; p-value = 0.0001). Tumors from early onset patients also showed higher prevalence of another mutational signature with unknown etiology (19% &amp;lt;40y, 16% 40-49y, 13% 50-59y, 6% 60-69y, 7% ≥70y, p-value = 0.005). Conclusions: These results indicate a potential association between SBS88 with early onset CRC, suggesting that the recent increase in incidence may be at least partially explained by the genotoxic compound colibactin, and associated bacteria. Citation Format: Wellington dos Santos, Marcos Diaz-Gay, Sarah Moody, Sergey Senkin, Behnoush Abedi-Ardekani, Mariya Kazachkova, Stephen Fitzgerald, Saamin Cheema, Valerie Gaborieau, Jingwei Wang, Christine Carreira, Thomas Cattiaux, Priscilia Chopard, Calli Latimer, David Zaridze, Riley Cox, Reza Malekzadeh, Miodrag Ognjanovic, Suleeporn Sangrajrang, Maria P. Curado, Rui M. Reis, Ivana Holcatova, Carlos Vaccaro, Beata Swiatkowska, Jolanta Lissowska, Carolina Wiesner, Tatsuhiro Shibata, Surasak Sangkhathat, Patricia Ashton-Prolla, Laura Humphreys, Sandra Perdomo, Ana C. de Caravalho, Mike Stratton, Paul Brennan, Ludmil Alexandrov. Mutational signatures in colorectal cancer from 11 countries reveal new insights in early-onset colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB134.

Unraveling the complexities of early-onset colorectal cancer: a perspective on dietary and microbial influences.

While advances in screening have resulted in declining rates of colorectal cancer (CRC) among adults ≥50 years of age since the mid-2000s, the incidence of early-onset CRC (EOCRC) has steadily increased over the last decade. This increase is not fully accounted for by hereditary factors, and the hypothesis that a sedentary lifestyle and obesity are the primary culprits is not fully supported by recent reports indicating that many affected individuals lead active lifestyles, maintain normal weight, and are otherwise healthy. Attention has shifted toward dietary patterns, notably the consumption of processed and ultra-processed foods found in Western diets, which are suspected of disrupting the gut microbiome balance that potentially leads to EOCRC. The impact of antibiotic use on the gut microbiome is also posited as a contributing factor, given its rising prevalence in medical and agricultural practices. We propose that a paradigm shift is necessary for EOCRC research, moving beyond metabolic factors to a broader exploration of dietary and microbial influences. Future research must prioritize understanding the relationship between dietary habits, particularly processed food intake, antibiotic exposure, and gut microbiome dynamics, to unravel the complex etiology of EOCRC. This will be crucial in developing comprehensive preventive strategies to address the increasing incidence of this malignancy in younger populations.

Obesity and Inflammatory Factors in the Progression of Early-Onset Colorectal Cancer.

Metabolic dysfunction associated with obesity leads to a chronic pro-inflammatory state with systemic effects, including the alteration of macrophage metabolism. Tumor-associated macrophages have been linked to the formation of cancer through the production of metabolites such as itaconate. Itaconate downregulates peroxisome proliferator-activated receptor gamma as a tumor-suppressing factor and upregulates anti-inflammatory cytokines in M2-like macrophages. Similarly, leptin and adiponectin also influence macrophage cytokine expression and contribute to the progression of colorectal cancer via changes in gene expression within the PI3K/AKT pathway. This pathway influences cell proliferation, differentiation, and tumorigenesis. This work provides a review of obesity-related hormones and inflammatory mechanisms leading to the development and progression of early-onset colorectal cancer (EOCRC). A literature search was performed using the PubMed and Cochrane databases to identify studies related to obesity and EOCRC, with keywords including 'EOCRC', 'obesity', 'obesity-related hormones', 'itaconate', 'adiponectin', 'leptin', 'M2a macrophage', and 'microbiome'. With this concept of pro-inflammatory markers contributing to EOCRC, increased use of chemo-preventative agents such as aspirin may have a protective effect. Elucidating this association between obesity-related, hormone/cytokine-driven inflammatory effects with EOCRC may help lead to new therapeutic targets in preventing and treating EOCRC.

A new clinical model for predicting lymph node metastasis in T1 colorectal cancer

PurposeLymph node metastasis (LNM) is a crucial factor that determines the prognosis of T1 colorectal cancer (CRC) patients. We aimed to develop a practical prediction model for LNM in T1 CRC.MethodsWe conducted a retrospective analysis of data from 825 patients with T1 CRC who underwent radical resection at a single center in China. All enrolled patients were randomly divided into a training set and a validation set at a ratio of 7:3 using R software. Risk factors for LNM were identified through multivariate logistic regression analyses. Subsequently, a prediction model was developed using the selected variables.ResultsThe lymph node metastasis (LNM) rate was 10.1% in the training cohort and 9.3% in the validation cohort. In the training set, risk factors for LNM in T1 CRC were identified, including depressed endoscopic gross appearance, sex, submucosal invasion combined with tumor grade (DSI-TG), lymphovascular invasion (LVI), and tumor budding. LVI emerged as the most potent predictor for LNM. The prediction model based on these factors exhibited good discrimination ability in the validation sets (AUC: 79.3%). Compared to current guidelines, the model could potentially reduce over-surgery by 48.9%. Interestingly, we observed that sex had a differential impact on LNM between early-onset and late-onset CRC patients.ConclusionsWe developed a clinical prediction model for LNM in T1 CRC using five factors that are easily accessible in clinical practice. The model has better predictive performance and practicality than the current guidelines and can assist clinicians in making treatment decisions for T1 CRC patients.

Nomogram model for predicting cancer-specific mortality in patients with early-onset colorectal cancer: a competing risk analysis insight from the SEER database and an external validation cohort.

Early-onset colorectal cancer (EOCRC) is increasing in incidence and poses a growing threat. Urgent research is needed, especially in survival analysis, to enhance comprehension and treatment strategies. This study aimed to explore the risk factors associated with cancer-specific mortality (CSM) and other-cause mortality (OCM) in patients with EOCRC. Additionally, the study aimed to develop a nomogram predicting CSM using a competitive risk model and validate its accuracy through the use of training, using internal and external cohorts. Data from EOCRC patients were collected from the Surveillance, Epidemiology, and End Results (SEER) database (2008-2017). EOCRC patients who were treated at a tertiary hospital in northeast China between 2014 and 2020 were also included in the study. The SEER data were divided into the training and validation sets at a 7:3 ratio. A univariate Cox regression model was employed to identify prognostic factors. Subsequently, multivariate Cox regression models were applied to ascertain the presence of independent risk factors. A nomogram was generated to visualize the results, which were evaluated using the concordance index (C-index), area under the curve (AUC), and calibration curves. The clinical utility was assessed via decision curve analysis (DCA). Multivariable Cox regression analysis demonstrated that factors such as race, tumor differentiation, levels of carcinoembryonic antigen (CEA), marital status, histological type, American Joint Committee on Cancer (AJCC) stage, and surgical status were independent risk factors for CSM in EOCRC patients. In addition, age, gender, chemotherapy details, CEA levels, marital status, and AJCC stage were established as independent risk factors for OCM in individuals diagnosed with EOCRC. A nomogram was developed using the identified independent risk factors, demonstrating excellent performance with a C-index of 0.806, 0.801, and 0.810 for the training, internal validation, and external validation cohorts, respectively. The calibration curves and AUC further confirmed the accuracy and discriminative ability of the nomogram. Furthermore, the DCA results indicated that the model had good clinical value. In this study, a competing risk model for CSM was developed in EOCRC patients. The model demonstrates a high level of predictive accuracy, providing valuable insights into the treatment decision-making process.

Risk Factors of Early Age Colorectal Cancer among Patients Attending at National Institute of Cancer Research &amp; Hospital

Background: Colorectal cancer (CRC) poses a significant public health burden worldwide, with a notable trend of increasing incidence among individuals aged 20 to 50 years. Understanding the risk factors associated with early-onset CRC is crucial for developing targeted prevention and intervention strategies, particularly in limited-resource settings. Objective: This study aimed to identify and analyze the risk factors contributing to the development of early-onset CRC in a population from a limited-resource country. Method: A comparative study was conducted among 178 CRC patients admitted to the National Institute of Cancer Research &amp; Hospital (NICRH), Dhaka. Patients were divided into two groups: Group-A (age 20-50 years) and Group-B (age &gt;50 years). Demographic and clinical data were collected, and statistical analyses were performed to determine associations between various risk factors and early-onset CRC. Results: The mean age of Group-A subjects was 43.6±7.1 years, significantly younger than Group-B subjects (59.2±9.3 years). Male patients constituted 69.1% of the cohort, with a statistically significant male-to-female ratio of 2.2:1. Higher BMI (≥25) was strongly associated with early-onset CRC (p&lt;0.01). Occupations such as business and middle socioeconomic status were significantly linked to early-onset CRC. Regular exercise (&gt;30 minutes daily) demonstrated a protective effect against CRC development. Consumption of red meat and fast food was associated with a higher risk of CRC, while regular consumption of vegetables was protective. Familial adenomatous polyposis (FAP) presence was significantly associated with early-onset CRC. Conclusions: Male sex, high BMI, specific occupations, dietary factors, and presence of FAP emerged as key risk factors for early-onset CRC. Encouraging regular exercise and promoting healthy dietary habits, particularly reducing red meat and fast-food intake, are crucial in mitigating the risk of early-onset CRC in similar populations.

Sexual Functioning and Impact on Quality of Life in Patients with Early-Onset Colorectal Cancer: A Systematic Review.

This systematic review investigates the intersection of early-onset colorectal cancer (EOCRC), sexual functioning, and associated quality of life (QoL), aiming to understand the comprehensive impact of EOCRC on these critical dimensions. Through an extensive search across PubMed, Scopus, and Embase up until November 2023, this study synthesized evidence from the literature while adhering to PRISMA guidelines. The studies included EOCRC patients under 50 years, which examined sexual functioning and QoL using validated instruments, and were published in English. After a rigorous screening process, five relevant studies were identified from an initial pool of 2184 articles. This review includes data from five studies involving 2031 EOCRC patients. The key findings revealed a high prevalence of sexual dysfunction, with up to 50% of men experiencing impotence and 58% reporting sexual dysfunction, alongside 36% of women in some studies. Pain was described by 12% to 31% of patients. Anxiety and depression were notably prevalent, affecting up to 69% of participants. EOCRC profoundly impacts sexual functioning and QoL, with a significant prevalence of sexual dysfunction and psychological distress among affected individuals. These findings suggest the need for oncological management strategies that include not only medical treatment but also psychological support and sexual health interventions. This systematic review emphasizes the importance of holistic patient care approaches, advocating for further research and clinical attention to address the complex needs of younger EOCRC patients.