Temporal Trends in Racial and Gender Disparities of Early Onset Colorectal Cancer in the United States: An Analysis of the CDC WONDER Database.

BACKGROUND: The mortality rates of early-onset colorectal cancer (EOCRC) have surged globally over the past two decades. While the underlying reasons remain largely unknown, understanding its epidemiology is crucial to address this escalating trend. This study aimed to identify disparities potentially influencing these rates, enhancing risk assessment tools, and highlighting areas necessitating further research. METHODS: Using the CDC Wide-Ranging Online Data for Epidemiologic Research (WONDER) database, this study assessed EOCRC mortality data from 2012 to 2020. Individuals under 50 years who succumbed to EOCRC were identified through the International Classification of Diseases, Tenth Revision (ICD-10) codes. Data interpretation and representation were performed using R 4.2.2 software. RESULTS: Between 2012 and 2020, EOCRC mortality rates fluctuated marginally between 1.7 and 1.8 per 100,000. Male mortality rates increased from 1.9 to 2.0 per 100,000, while female rates varied between 1.5 and 1.6 per 100,000. Significant variations were observed across age groups, with the 40-49 years category experiencing an increase from 6.34 (2012) to 6.94 (2020) per 100,000. Racial category-based data revealed the highest mortality rates among African Americans. Geographically, Mississippi and Alabama exhibited elevated mortality rates. Age-adjusted mortality rate (AAMR) assessments indicated a marked decline for both genders from 2012 to 2020, with consistently higher rates for men. CONCLUSION: The findings highlight the evolving landscape of EOCRC mortality, revealing significant gender, age, and racial disparities. These results underscore the urgent need for tailored health strategies and intensified research efforts targeting these disparities.

Could environmental exposure and climate change Be a key factor in the rising incidence of early onset colorectal cancer?

The emergence of early onset colorectal cancer (EOCRC) is believed to result from the complex interplay between external environmental factors and internal molecular processes. This review investigates the potential association between environmental exposure to chemicals and climate change and the increased incidence of EOCRC, focusing on their effects on gut microbiota (GM) dynamics. The manuscript explores the birth cohort effect, suggesting that individuals born after 1950 may be at higher risk of developing EOCRC due to cumulative environmental exposures. Furthermore, we also reviewed the impact of environmental pollution, including particulate matter and endocrine disrupting chemicals (EDCs), as well as global warming, on GM disturbance. Environmental exposures have the potential to disrupt GM composition and diversity, leading to dysbiosis, chronic inflammation, and oxidative stress, which are known risk factors associated with EOCRC. Particulate matter can enter the gastrointestinal tract, modifying GM composition and promoting the proliferation of pathogenic bacteria while diminishing beneficial bacteria. Similarly, EDCs, can induce GM alterations and inflammation, further increasing the risk of EOCRC. Additionally, global warming can influence GM through shifts in gut environmental conditions, affecting the host's immune response and potentially increasing EOCRC risk. To summarize, environmental exposure to chemicals and climate change since 1950 has been implicated as contributing factors to the rising incidence of EOCRC. Disruptions in gut microbiota homeostasis play a crucial role in mediating these associations. Consequently, there is a pressing need for enhanced environmental policies aimed at minimizing exposure to pollutants, safeguarding public health, and mitigating the burden of EOCRC.

When the vermiform appendix resembles a polyp: Be cautious of an intussuscepted appendix polypectomy.

This article discusses a recently published case report on a rare instance of type IV appendiceal intussusception with a concurrent mucinous adenocarcinoma of the cecum in a young individual. The report highlights challenges in diagnosing appendiceal intussusception, emphasizing the importance of endoscopic expertise in preventing impulsive decisions such as inappropriate polypectomies. The rarity of the concurrent intussuscepted appendix and mucinous cecal cancer is underscored, prompting consideration of malignancy in appendiceal intussusception cases. Additionally, the report addresses the increasing incidence of early-onset colorectal cancer and the need for a revaluation of diagnostic paradigms in the context of evolving epidemiological trends. The awareness of potential misinterpretations and the imperative for further investigation into this rare condition are emphasized.

Sex differences in survival outcomes of early-onset colorectal cancer.

Colorectal cancer (CRC) is one of the most fatal cancers in the United States. Although the overall incidence and mortality rates are declining, an alarming rise in early-onset colorectal cancer (EOCRC), defined as CRC diagnosis in patients aged < 50 years, was previously reported. Our study focuses on analyzing sex-specific differences in survival among EOCRC patients and comparing sex-specific predictors of survival in both males and females in the United States. We retrieved and utilized data from the Surveillance, Epidemiology, and End Results (SEER) program. EOCRC patients, between the ages of 20 and 49, were exclusively included. We conducted thorough survival analyses using Kaplan-Meier curves, log-rank tests, Cox regression models, and propensity score matching to control for potential biases. Our study included 58,667 EOCRC patients (27,662 females, 31,005 males) diagnosed between 2000 and 2017. The baseline characteristics at the time of diagnosis were significantly heterogeneous between males and females. Males exhibited significantly worse overall survival (OS), cancer-specific survival (CSS), and noncancer-specific survival (NCSS) in comparison to females in both the general cohort, and the matched cohort. Predictors of survival outcomes generally followed a similar pattern in both sexes except for minor differences. In conclusion, we identified sex as an independent prognostic factor of EOCRC, suggesting disparities in survival between sexes. Further understanding of the epidemiological and genetic bases of these differences could facilitate targeted, personalized therapeutic approaches for EOCRC.

A Systematic Review of Diagnostic Performance of Circulating MicroRNAs in Colorectal Cancer Detection with a Focus on Early-Onset Colorectal Cancer.

The rising incidence and mortality of early-onset colorectal cancer (EOCRC) emphasize the urgent need for effective non-invasive screening. Circulating microRNAs (miRNAs) have emerged as promising biomarkers for cancer detection. This systematic review aims to evaluate the diagnostic performance of circulating miRNAs in detecting colorectal cancer (CRC). A literature search was conducted in PubMed and Scopus. Studies that report sensitivity, specificity, or area under the curve (AUC) for CRC detection by miRNA were included. The miRNA miR-21 was the most frequently studied biomarker, with a varying range of AUC from 0.55 to 0.973 attributed to differences in study populations and methodologies. The miRNAs miR-210 and miR-1246 showed potential diagnostic capacity with miR-1246 achieving an AUC of 0.924, 100% sensitivity, and 80% specificity. The miRNA panels offer improved diagnostic performance compared to individual miRNA. The best performing panel for CRC patients below 50 is miR-211 + miR-25 + TGF-ß1 with AUC 0.99 and 100 specificity and 97 sensitivity. Circulating miRNAs hold significant promise as non-invasive biomarkers for CRC screening. However, the variability in diagnostic performance highlights the need for a standardized method and robust validation studies. Future research should focus on large-scale, ethnically diverse cohorts to establish clinically relevant miRNA biomarkers for CRC, particularly in younger populations.

Associations between blood glucose and early- and late-onset colorectal cancer: evidence from two prospective cohorts and Mendelian randomization analyses.

Background: The incidence of early-onset colorectal cancer (EOCRC), which exhibits differential clinical, pathological, and molecular features compared to late-onset CRC (LOCRC), is rising globally. The potential differential effects of blood glucose on EOCRC compared to LOCRC have not been investigated. Methods: This study analyzed 374,568 participants from the UK Biobank cohort and 172,809 participants from the Kailuan cohort. The linear associations between blood glucose and EOCRC/LOCRC were estimated using Cox regression models. Restricted cubic spline (RCS) analysis and non-linear Mendelian randomization (MR) analysis using a 70-SNPs genetic instrument for fasting glucose were used to explore the potential non-linear associations. Results: Participants in the highest quintile of blood glucose had higher overall CRC risk compared to the lowest quintile (HR = 1.10 in the UK Biobank cohort, 95% CI: 1.01-1.21, P-trend = 0.012; HR = 1.23 in the Kailuan cohort, 95% CI: 1.01-1.51, P-trend = 0.036). Elevated glucose (>7.0 mmol/L) was more strongly associated with increased risk of EOCRC (HR = 1.61, 95% CI: 1.07-2.44) than with LOCRC (HR = 1.14, 95% CI: 1.02-1.27) in the UK Biobank cohort (P-heterogeneity = 0.014). Elevated glucose (>7.0 mmol/L) was associated with increased risk of LOCRC (HR = 1.25, 95% CI: 1.04-1.65) in the Kailuan cohort as well. There was no evidence for non-linear associations between blood glucose and risks of EOCRC/LOCRC. Conclusions: This study showed a positive association between blood glucose and CRC risk in a dose-response manner, particularly for EOCRC, suggesting that tighter glucose control should be a priority for younger age groups.

Impact of time period and birth cohort on the trend of advanced neoplasm prevalence in the 40-49 average-risk screening population.

BACKGROUND AND AIMS: Early-onset colorectal cancer (CRC) is increasing globally. While the United States have lowered the age of initiation of screening to 45, other countries still start screening at age 50. In Taiwan, the incidence of CRC has declined in 55-74 year-olds after the initiation of screening, but still increased in those 50-54, potentially due to rising precancerous lesion incidence in 40-49 year-olds. This study aimed to explore the chronological trend of the prevalence of colorectal advanced neoplasms (AN) in the screening population aged 40-54. METHODS: We retrospectively analyzed a screening colonoscopy cohort for prevalence of AN in average-risk subjects aged 40-54 from 2003 to 2019. Logistic regression was used to distinguish cohort effect from time-period effect on the prevalence of AN. RESULTS: In total, 27,805 subjects (52.1% male) men were enrolled. There were notable increases in prevalence of AN in all three age groups during the 17-year span, but these were more rapid in age 40-44 (0.99% to 3.22%) and 45-49 (2.50% to 4.19%). Age 50-54 had higher risk of AN [aOR=1.62(1.19-2.19)] in 2003-2008 but not in later periods [2009-2014: aOR=1.08(0.83-1.41)] and [2015-2019: aOR=0.76(0.56-1.03)] when compared with age 45-49. CONCLUSION: The prevalence of AN in age 40-54 increased in the Taiwanese population, with a later birth cohort having a higher prevalence of AN. However, the prevalence of AN in age 45-49 increased more remarkably and approximated that in age 50-54, which may justify earlier initiation of CRC screening at age 45.

Early-Onset colorectal Cancer: From the laboratory to the clinic.

Colorectal cancer that occurs before age of 50 is defined as Early-Onset Colorectal Cancer (EOCRC). Its incidence has worryingly increased since the late 90 s and is expected to keep rising in the next future, despite Late-Onset CRC (LOCRC) is decreasing worldwide. Because of this, there is an urgent need to better understand this subset of patients in order to give them the best treatment possible. However, most of the literature is retrospective and often discordant. In this review, we aim to provide a general overview of the issue, endeavoring to highlight the current available knowledge. We decided to move from the beginning, investigating risk factors and inheritance, passing through diagnosis and clinical aspects, and to conclude with the translational part, focusing on the biology of the tumor. However, lot of questions remain open, including screening age and prognosis. Indeed, young patients tend to be treated more aggressively, even if a survival benefit has not been proven yet. Every clinician should be aware of the best practice for young people, and more translational studies are awaited in order to clarify is EOCRC represents a distinct biological entity.

Heterogeneity in survival within age groups of early-onset colorectal cancer patients: A National Cancer Database analysis.

BACKGROUND: We aimed to identify predictors of and heterogeneity in survival among different age groups of patients with early-onset colorectal cancer (EOCRC). METHODS: This retrospective cohort study used National Cancer Database data from 2004 to 2019. Differences in survival among CRC patients <50 years, subcategorized into age groups (<20, 20-29, 30-39, 40-49 years) were compared for demographic, clinical, and histologic features by univariate and multivariate analyses. Cox hazard regression and Kaplan Meier survival analysis were performed. RESULTS: 134 219 of the 1 240 787 individuals with CRC (10.8%) were <50 years old; 46 639 (34.8%) had rectal and 87 580 (65.3%) had colon cancer. Within the colon cancer cohort, individuals aged between 30 and 39 years had the highest overall survival rate (66.7%) during a median follow-up of 47.6 months (interquartile range IQR 23.1-89.7). The same age group in the rectal cancer cohort had the lowest survival rate (31%) over a median follow-up of 54.5 (IQR 28.24-97.31) months. Leading factors affecting survival included tumor stage (HR 8.23 [4.64-14.6]; p < 0.0001), lymphovascular invasion (HR 1.88 [1.70-2.06]; p < 0.0001) and perineural invasion (HR 1.08 [1.02-1.15]; p = 0.001). CONCLUSION: Survival trends vary within age groups of patients affected with early onset colon cancer compared to rectal cancer. Tumor stage and unfavorable pathological characteristics are the strongest factors predicting survival.

Advancing early onset colorectal cancer research: research advocacy, health disparities, and scientific imperatives.

Early onset colorectal cancer (EOCRC) emerged as the fourth foremost contributor to cancer-related mortality among both genders in the late 1990s. Presently, EOCRC (<50) ranks as the leading cause of cancer mortality in men and the second leading cause in women within the United States. Similar trends are now also evident globally, particularly in developed countries. Furthermore, there is strong evidence confirming that health disparities persist in the diagnosis and treatment of EOCRC, with signs indicating that these gaps may worsen in specific cases. These alarming trends highlight the critical need for research to inform evidence-based interventions to reduce the burden of EOCRC globally. Fight Colorectal Cancer (Fight CRC) is the leading patient advocacy group in the United States providing information on colon and rectal cancer research, prevention, treatment, and policy. It is the opinion of Fight CRC that an international, coordinated effort with the medical, research, scientific, advocacy, industry and funding community is needed to advance impactful research. Fight CRC, in partnership with José Perea, MD, PhD, of the Institute of Biomedical Research of Salamanca (IBSAL) in Spain, and partners, are working together to address this global phenomenon and are presenting a multi-faceted research approach to move the field forward.

Young-Onset Rectal Cancer: Is It for Real?

The incidence of early-onset colorectal cancer has been rising over the last two decades. Tumors in young patients have distinct features compared to older patients. They predominantly arise in the distal colon and rectum and have poor histological features. Patients tend to present at a more advanced stage and be exposed to more aggressive management approaches; however, this has not translated into a significant survival benefit compared to their older counterparts. This chapter will share current evidence on risk factors and management options for early onset colorectal cancer with a focus on rectal cancer.

Randomized control trial of moderate dose vitamin D alters microbiota stability and metabolite networks in healthy adults.

Evidence indicates that both vitamin D and the gut microbiome are involved in the process of colon carcinogenesis. However, it is unclear what effects supplemental vitamin D3 has on the gut microbiome and its metabolites in healthy adults. We conducted a double-blind, randomized, placebo-controlled trial to identify the acute and long-term microbiota structural and metabolite changes that occur in response to a moderate dose (4,000 IU) of vitamin D3 for 12 weeks in healthy adults. Our results demonstrated a significant increase in serum 25-hydroxy-vitamin D (25(OH)D) in the treatment group compared to placebo (P < 0.0001). Vitamin D3 significantly increased compositional similarity (P < 0.0001) in the treatment group, and enriched members of the Bifidobacteriaceae family. We also identified a significant inverse relationship between the percent change in serum 25(OH)D and microbial stability in the treatment group (R = -0.52, P < 0.019). Furthermore, vitamin D3 supplementation resulted in notable metabolic shifts, in addition to resulting in a drastic rewiring of key gut microbial-metabolic associations. In conclusion, we show that a moderate dose of vitamin D3 among healthy adults has unique acute and persistent effects on the fecal microbiota, and suggest novel mechanisms by which vitamin D may affect the host-microbiota relationship. IMPORTANCE: Preventative measures to reduce the rise in early-onset colorectal cancer are of critical need. Both vitamin D, dietary and serum levels, and the gut microbiome are implicated in the etiology of colorectal cancer. By understanding the intimate relationship between vitamin D, the gut microbiome, and its metabolites, we may be able to identify key mechanisms that can be targeted for intervention, including inflammation and metabolic dysfunction. Furthermore, the similarity of vitamin D to cholesterol, which is metabolized by the gut microbiome, gives precedence to its ability to produce metabolites that can be further studied and leveraged for controlling colorectal cancer incidence and mortality.

Challenges around diagnosis of early onset colorectal cancer, and the case for screening.

BACKGROUND: Colorectal cancer (CRC) is the third most diagnosed cancer in the world, with an estimated 1.93 million cases diagnosed in 2020. While the overall CRC incidence in many countries is falling there has been a dramatic increase in CRC in those aged under 50 (early onset colorectal cancer, EOCRC). The reason for this increase in EOCRC is unknown. As the best predictor of survival is stage at diagnosis, early diagnosis is likely to be beneficial and population screening may facilitate this. METHODS: A narrative review of the literature was undertaken. RESULTS: Improving time to diagnosis in symptomatic patients is beneficial. However, by the time symptoms develop, over a third of patients already have metastatic disease. Screening asymptomatic patients (with Faecal Immunochemical test (FIT) and colonoscopy) has been proved to be effective in older patients (>60 years). In younger populations, the decreasing incidence rates of CRC previously made cost effectiveness, compliance and therefore benefit questionable. Now, with the increasing incidence of CRC in those under 50 years of age, modelling suggests screening with FIT and colonoscopy is cost effective from 40 years of age. There is evidence that some countries screening below 50 have prevented the rise in EOCRC incidence. Additionally the use of new and novel non-invasive biomarkers may also be able to improve the accuracy of screening asymptomatic patients. CONCLUSION: Diagnosis of EOCRC once symptoms develop is often too late, and screening patients from age 40 is the best way to improve outcomes in this group.

CRCDB: A comprehensive database for integrating and analyzing multi-omics data of early-onset and late-onset colorectal cancer.

The incidence of early-onset colorectal cancer (EOCRC) has increased significantly worldwide. Uncovering biomarkers that are unique to EOCRC is of great importance to facilitate the prevention and detection of this growing cancer subtype. Although efforts have been made in the data curation about CRC, there is no integrated platform that gives access to data specifically related to young CRC patients. Here, we constructed a user-friendly open integrated resource called CRCDB (URL: http://crcdb-hust.com) which contains multi-omics data of 785 EOCRC, 4898 late-onset CRCs (LOCRC), and 1110 normal control samples from tissue, whole blood, platelets, and serum exosomes. CRCDB manages the differential analysis, survival analysis, co-expression analysis, and immune cell infiltration comparison analysis results in different CRC groups. Meta-analysis results were also provided for users for further data interpretation. Using the resource in CRCDB, we identified that genes associated with the metabolic process were less expressed in EOCRC patients, while up regulated genes most associated with the mitosis process might play an important role in the molecular pathogenesis of LOCRC. Survival-related genes were most enriched in oxidoreduction pathways in EOCRC while in immune-related pathways in LOCRC. With all the data gathered and processed, we anticipate that CRCDB could be a practical data mining platform to help explore potential applications of omics data and develop effective prevention and therapeutic strategies for the specific group of CRC patients.

Global incidence trends of early-onset colorectal cancer and related exposures in early-life: an ecological analysis based on the GBD 2019.

Background: The incidence of early-onset colorectal cancer (EOCRC) is increasing globally. This study aims to describe the temporal trends of incidence and explore related risk exposures in early-life at the country level based on the GBD 2019. Methods: Data on the incidence and attributable risk factors of EOCRC were obtained from the GBD 2019. Temporal trends of age-standardized incidence were evaluated by average annual percentage change (AAPC). Early-life exposures were indicated as summary exposure values (SEV) of selected factors, SDI and GDP per capita in previous decades and at ages 0-4, 5-9, 10-14 and 15-19 years. Weighted linear or non-linear regressions were applied to evaluate the ecological aggregate associations of the exposures with incidences of EOCRC. Results: The global age-standardized incidence of EOCRC increased from 3.05 (3.03, 3.07) to 3.85 (3.83, 3.86) per 100,000 during 1990 and 2019. The incidence was higher in countries with high socioeconomic levels, and increased drastically in countries in East Asia and Caribbean, particularly Jamaica, Saudi Arabia and Vietnam. The GDP per capita, SDI, and SEVs of iron deficiency, alcohol use, high body-mass index, and child growth failure in earlier years were more closely related with the incidences of EOCRC in 2019. Exposures at ages 0-4, 5-9, 10-14 and 15-19 years were also associated with the incidences, particularly for the exposures at ages 15-19 years. Conclusion: The global incidence of EOCRC increased during past three decades. The large variations at regional and national level may be related with the distribution of risk exposures in early life.

Markers of Epithelial-Mesenchymal Transition and Mucinous Histology Are Significant Predictors of Disease Severity and Tumor Characteristics in Early-Onset Colorectal Cancer.

Approximately 20% of patients with colorectal cancer (CRC) are diagnosed with a mucinous subtype of this tumor, have a worse prognosis, and often show resistance to available therapies. Molecules from the mucin family are involved in the regulation of epithelial-mesenchymal transition (EMT), which significantly determines the cancer aggressiveness. This study aimed to examine the diagnostic and prognostic significance of mucinous histology and EMT markers in patients with early-onset CRC and their association with disease severity and tumor characteristics. This study included tumor tissue samples from 106 patients diagnosed with CRC before the age of 45, 53 with mucinous and 53 with non-mucinous tumors. The EMT status was determined by immunohistochemical analysis of E-cadherin and Vimentin in tissue sections. Mucinous tumors had significantly higher Mucin-1 (p < 0.001) and cytoplasmic E-cadherin (p = 0.043) scores; they were significantly less differentiated (p = 0.007), more advanced (p = 0.027), and predominately affected right the colon (p = 0.039) compared to non-mucinous tumors. Epithelial tumors were significantly better differentiated (p = 0.034) and with less prominent tumor budding (p < 0.001) than mesenchymal tumors. Mucin-1 and Vimentin were independent predictors of tumor differentiation (p = 0.006) and budding (p = 0.001), respectively. Mucinous histology and EMT markers are significant predictors of disease severity and tumor characteristics in early-onset colorectal cancer.

Early onset colorectal cancer: Cancer promotion in young tissue.

The incidence of colorectal cancer (CRC) in patients under 50 has been increasing over the past several decades. The factors underlying the increase in early onset colorectal cancer (EOCRC) are not entirely clear, although several genetic and clinical differences with late onset colorectal cancer (LOCRC) have been noted. EOCRC cases are often diagnosed at a more advanced stage, raising the possibility that these cancers progress more rapidly than LOCRC cases. The impact of age on cancer progression is an intriguing topic and numerous lines of research have found that a young tissue environment is often more promotional. In fact, a less hospitable promotional tissue environment in older individuals may offset the increased cancer risk associated with the increased mutational load associated with age. Here we address how youthful aspects of angiogenesis, the tumor immune response, and the oxidative stress response may contribute to the rapid progression of EOCRC. Understanding the factors promoting EOCRC may provide insight into why EOCRC cases are increasing.

Survival Analysis of Metastatic Early-Onset Colorectal Cancer Compared to Metastatic Average-Onset Colorectal Cancer: A SEER Database Analysis.

BACKGROUND: Early-onset colorectal cancer (EO-CRC) is defined as colorectal cancer diagnosed before the age of 50 years, and its incidence has been increasing over the last decade, now accounting for 10% of all new CRC diagnoses. Average-onset colorectal cancer (AO-CRC) has shown a steady decline in its incidence and related mortality over the past 20 years. The disparities in outcomes and overall survival (OS) between EO-CRC and AO-CRC are controversial. Our study compared OS and cause-specific survival (CSS) between metastatic EO-CRC (mEO-CRC) and metastatic AO-CRC (mAO-CRC) and identified the associated factors. METHODS: Data on patient characteristics, tumor characteristics, incidence, and mortality were obtained from the SEER database from 2010 to 2020. We identified 23,278 individuals aged > 18 years with a confirmed diagnosis of all histological subtypes of metastatic CRC (M1 on TNM stage) using ICD-O-3 site codes. mEO-CRC and mAO-CRC were compared. OS distributions and CCS were analyzed using the Kaplan-Meier method and log-rank test to assess differences. A Cox regression model was used to assess the associations between variables. RESULTS: mEO-CRC constituted 17.79% of the cases, whereas 82.21% had mAO-CRC. Most patients with mEO-CRC were 45-49 years old (47.66%), male (52.16%) and White (72.57%) and had adenocarcinoma histology (87.30%). Left colon tumors were most prevalent in both groups (40.26%) but were more prevalent in mEO-CRC patients than in mAO-CRC patients (49.63% vs. 38.23%, p < 0.001). Patients with mEO-CRC had higher OS (p < 0.001) and CSS (p < 0.001) than those with mAO-CRC. Patients with mEO-CRC also had significantly better median overall survival (30 months vs. 18 months, p < 0.001). The factors associated with worse OS included mAO-CRC (p < 0.001), mucinous adenocarcinoma (p < 0.001), male sex (p = 0.003), and a lack of surgical intervention (p < 0.001). CONCLUSIONS: Most patients with mEO-CRC fall within the range of 45 to 49 years of age. Patients with mEO-CRC were more likely to receive cancer-directed therapy (including chemotherapy and radiotherapy) and had better OS and CSS than those with mAO-CRC. This is likely attributable to the better performance status, fewer comorbidities, and better tolerance to cancer-directed therapy in mEO-CRC patients. The factors associated with worse OS and CSS were age > 50 years, mucinous adenocarcinoma, male sex, and no surgical treatment.

A Survey Detailing Early Onset Colorectal Cancer Patient and Caregiver Experiences in Canada.

The incidence of early onset colorectal cancer (EOCRC) in Canada has increased. To address the growing incidence of EOCRC, Colorectal Cancer Canada (CCC) developed the Never Too Young (N2Y) program to identify gaps in care and evaluate patient and caregiver experiences with CRC. The survey was available online using SurveyMonkey across Canada between 12 December 2022 and 1 May 2023. The patient and caregiver survey consisted of 113 and 94 questions, respectively. A total of 108 EOCRC patients and 20 caregivers completed the survey. Many respondents were unaware of EOCRC (41.6%) and the disease symptoms (45.2%) before diagnosis. Patient age at diagnosis was between 45 and 50 years in 31.7%, and 72.8% of them were diagnosed at stage III or IV. A perception of an initial misdiagnosis was common (67.4%) for EOCRC patients, and 51.2% felt dismissed due to their age. Patients and caregivers reported impacts of EOCRC on their mental health, with 70.9% of patients expressing a need for support with depression and 93.3% of caregivers experiencing a constant fear of recurrence of their loved one's cancer. Improving the Canadian population's awareness of EOCRC (e.g., CRC symptoms) is important for ensuring timely diagnoses. Similarly, it is critical to ensure that healthcare providers are aware of the increase in EOCRC cases and the unique needs of these patients. Re-evaluation of the CRC screening age should be undertaken in Canada to determine whether lowering the start age to 45 years will improve outcomes in this demographic.

Genomic and Transcriptomic Analysis of a Patient with Early-Onset Colorectal Cancer and Therapy-Induced Focal Nodular Hyperplasia: A Case Report.

Early-onset colorectal cancer (EOCRC), defined as colorectal cancer in individuals under 50 years of age, has shown an alarming increase in incidence worldwide. We report a case of a twenty-four-year-old female with a strong family history of colorectal cancer (CRC) but without an identified underlying genetic predisposition syndrome. Two years after primary surgery and adjuvant chemotherapy, the patient developed new liver lesions. Extensive diagnostic imaging was conducted to investigate suspected liver metastases, ultimately leading to a diagnosis of focal nodular hyperplasia. The young age of the patient has prompted comprehensive genomic and transcriptomic profiling in order to identify potential oncogenic drivers and inform further clinical management of the patient. Besides a number of oncogenic mutations identified in the patient's tumour sample, including KRAS G12D, TP53 R248W and TTN L28470V, we have also identified a homozygous deletion of 24.5 MB on chromosome 8. A multivariate Cox regression analysis of this patient's mutation profile conferred a favourable prognosis when compared with the TCGA COADREAD database. Notably, the identified deletion on chromosome 8 includes the WRN gene, which could contribute to the patient's overall positive response to chemotherapy. The complex clinical presentation, including the need for emergency surgery, early age at diagnosis, strong family history, and unexpected findings on surveillance imaging, necessitated a multidisciplinary approach involving medical, radiation, and surgical oncologists, along with psychological support and reproductive medicine specialists. Molecular profiling of the tumour strongly indicates that patients with complex mutational profile and rare genomic rearrangements require a prolonged surveillance and personalised informed interventions.