Incidence Of Young-onset Colorectal Cancer Research Articles

Development and validation of machine learning models for young-onset colorectal cancer risk stratification

Incidence of young-onset colorectal cancer (YOCRC, younger than 50) has significantly increased worldwide. The performance of fecal immunochemical test in detecting YOCRC is unsatisfactory. Using routine clinical data, we aimed to develop machine learning (ML) models to identify individuals with high-risk YOCRC who require further colonoscopy. We retrospectively extracted data of 10,874 young individuals. Multiple supervised ML techniques were devised to distinguish individuals with and without CRC, classifiers were trained, internally validated and temporally validated. In internal validation cohort, Random Forest (RF) ML model demonstrated good performance with AUC of 0.859 and highest recall of 0.840. In temporal validation cohort, the RF ML model also exhibited good classification performance, achieving AUC of 0.888 and highest recall of 0.872. RF algorithm-based approach is effective and feasible in YOCRC risk stratification. This could be valuable in assessing the risk of YOCRC so that clinical management, including further colonoscopy, can be subsequently made. (Registration: This study was registered with ClinicalTrials.gov (NCT06342622) on March 15, 2024.).

Consistent signatures in the human gut microbiome of old- and young-onset colorectal cancer

The incidence of young-onset colorectal cancer (yCRC) has been increasing in recent decades, but little is known about the gut microbiome of these patients. Most studies have focused on old-onset CRC (oCRC), and it remains unclear whether CRC signatures derived from old patients are valid in young patients. To address this, we assembled the largest yCRC gut metagenomes to date from two independent cohorts and found that the CRC microbiome had limited association with age across adulthood. Differential analysis revealed that well-known CRC-associated taxa, such as Clostridium symbiosum, Peptostreptococcus stomatis, Parvimonas micra and Hungatella hathewayi were significantly enriched (false discovery rate <0.05) in both old- and young-onset patients. Similar strain-level patterns of Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli were observed for oCRC and yCRC. Almost all oCRC-associated metagenomic pathways had directionally concordant changes in young patients. Importantly, CRC-associated virulence factors (fadA, bft) were enriched in both oCRC and yCRC compared to their respective controls. Moreover, the microbiome-based classification model had similar predication accuracy for CRC status in old- and young-onset patients, underscoring the consistency of microbial signatures across different age groups.

National Trends in the Incidence of Sporadic Malignant Colorectal Polyps in Young Patients (20-49 Years): An 18-Year SEER Database Analysis.

Background and Objectives: Conflicting guidelines exist for initiating average-risk colorectal cancer screening at the age of 45 years. The United States Preventive Services Task Force (USPSTF) changed its guidelines in 2021 to recommend initiating screening at 45 years due to an increasing incidence of young-onset colorectal cancer. However, the American College of Physicians (ACP) recently recommended not screening average-risk individuals between 45 and 49 years old. We aim to study the national trends in the incidence of sporadic malignant polyps (SMP) in patients from 20 to 49 years old. Materials and Methods: We analyzed the Surveillance, Epidemiology, and End Results database (2000-2017) on patients aged 20-49 years who underwent diagnostic colonoscopy with at least a single malignant sporadic colorectal polyp. Results: Of the 10,742 patients diagnosed with SMP, 42.9% were female. The mean age of incidence was 43.07 years (42.91-43.23, 95% CI). Approximately 50% of malignant polyps were diagnosed between 45 and 49 years of age, followed by 25-30% between 40 and 45. There was an upward trend in malignant polyps, with a decreased incidence of malignant villous adenomas and a rise in malignant adenomas and tubulovillous adenomas. Conclusions: Our findings suggest that almost half of the SMPs under 50 years occurred in individuals under age 45, younger than the current screening threshold recommended by the ACP. There has been an upward trend in malignant polyps in the last two decades. This reflects changes in tumor biology, and necessitates further research and support in the USPSTF guidelines to start screening at the age of 45 years.

Molecular Landscape and Therapeutic Strategies against Colorectal Cancer.

Colorectal cancer (CRC) is the second leading cause of cancer deaths worldwide. Although the overall incidence of CRC is decreasing, the incidence of young-onset CRC, characterized by a diagnosis of CRC before age 50, is increasing. Outcomes for CRC patients are improving, partly due to comprehensive molecular characterization of tumors and novel therapeutic strategies. Advances in genomic and transcriptomic analyses using blood- and tumor-tissue-based sequencing have facilitated identification of distinct tumor subtypes harboring unique biological characteristics and therapeutic vulnerabilities. These insights have led to the development and incorporation of targeted therapies and immunotherapy in CRC treatment. In this review, we discuss the molecular landscape and key oncogenes/tumor suppressors contributing to CRC tumorigenesis, metastasis, and therapeutic resistance. We also discuss personalized therapeutic strategies for subsets of CRC patients and provide an overview of evolving novel treatments being evaluated in clinical trials.

Sex-based differences in the transcriptomic metabolic profiling in young onset colorectal cancer (YOCRC).

155 Background: The incidence of YOCRC has been rising rapidly. We recently showed that the YOCRC population has significantly different transcriptional metabolic and immune profiles than their older counterparts. In a separate study, we found that the metabolic and immune environments are affected by the sex of the patient. Based on these findings, we hypothesize that significant differences in transcriptional metabolic and immune profiles of males and females exist within the YOCRC population. The primary objective of this study was to identify those differences and compare them with the average onset colorectal cancer (AOCRC) population. Methods: Using TCGA (YOCRC N=48) and ORIEN CRC (YOCRC N=96) datasets, patients were separated into younger onset (&lt;50) and older (&gt;60) patient populations, comparing male and female transcriptional programs within each of the age groups. Subsequently, their transcriptional profiles were compared and assessed via differential gene expression analysis (DESeq2), gene set enrichment analysis (GSEA), immune deconvolution (TIMER2.0), and metabolic pathway analysis (MetaPhOR). These pathways were then mapped to assess transcriptional dysregulation, and patterns of predicted metabolic flux. Results: Our analysis revealed different transcriptional, metabolic, and immune signatures between males and females in differing age groups. Amongst the young patients, females were enriched for lipid metabolism (cholesterol and steroid metabolism), decreased macrophage signatures, and a proliferative phenotype. Conversely, males were enriched for glucocorticoid metabolism, urea cycle metabolites, metastasis, and CD4+ T Cell populations. Further, CTLA4 and PD-L1 response signatures were decreased in young males compared to young females, with a notable increase in inflammatory pathways. Immune deconvolution revealed no difference in the predicted infiltration of immune cells between younger males and females. In older patients (&gt;60), females were enriched for lipid metabolism (testosterone, linoleic acid metabolism), CD8+ T cell signatures, and a proliferative phenotype. In contrast, males were enriched for lipid metabolism (cortisol), epigenetic alterations, and decreased macrophages. Like the younger population, CTLA4 and PD-L1 response signatures were decreased in older males, compared to older females, with a notable increase in inflammatory pathways. Immune deconvolution revealed decreases in CD8+ T cells and neutrophils in the predicted infiltration of older males' immune cells compared to older females. Conclusions: Our research revealed that the sex of the patient is associated with the transcriptional metabolic and immune profiles in YOCRC and AOCRC. Further translational research is needed to understand the biology better and develop effective, personalized treatment options.

Direct Medical Spending on Young and Average-Age Onset Colorectal Cancer before and after Diagnosis: a Population-Based Costing Study.

Despite a better understanding of the increasing incidence of young-onset colorectal cancer (yCRC; age at diagnosis <50 years), little is known about its economic burden. Therefore, we estimated direct medical spending on yCRC before and after diagnosis. We used linked administrative health databases in British Columbia, Canada, to create a study population of yCRC and average-age onset colorectal cancer (aCRC; age at diagnosis ≥50 years) cases, along with cancer-free controls. Over the 1-year period preceding a colorectal cancer diagnosis, we estimated direct medical spending on hospital visits, healthcare practitioners, and prescription medications. After diagnosis, we calculated cost attributable to yCRC and aCRC, which additionally included the cost of cancer treatments (e.g., chemotherapy and radiotherapy) across phases of care. We included 1,058 yCRC (45.4% females; age at diagnosis 42.4 ± 6.2 years) and 12,619 aCRC (44.8% females; age at diagnosis of 68.1 ± 9.2 years) cases. Direct medical spending on the average yCRC and aCRC case during the year before diagnosis was $6,711 and $8,056, respectively. After diagnosis, the overall average annualized cost attributable to yCRC significantly differed in comparison with aCRC for the initial ($50,216 vs. $37,842; P < 0.001), continuing ($8,361 vs. $5,014; P < 0.001), and end-of-life cancer phase ($86,125 vs. $61,512; P < 0.001) but not end-of-life non-cancer phase ($77,273 vs. $23,316; P = 0.372). Reported cost estimates may be used as inputs for future economic evaluations pertaining to yCRC. We provided comprehensive cost estimates for healthcare spending on young-onset colorectal cancer.

Metabolomic differences in young-onset versus average-onset colorectal adenocarcinoma.

3510 Background: Novel deleterious effects of environmental exposures may play a role in the rising incidence of young-onset colorectal cancer (yoCRC). We used metabolomics to assess differences between yoCRC and average-onset CRC (aoCRC), in comparison to healthy controls, which may provide insight into the pathogenesis and suggest any exposure risks. Methods: Patients with stage I-IV CRC and healthy controls were identified from prospective biobanks and categorized based on age &lt; 50 years (yoCRC or young controls) or age &gt; 60 years (aoCRC or older controls). Plasma metabolites were profiled using GC-TOF mass spectrometry. Differential abundance of metabolites was investigated using unadjusted and adjusted logistic regression. Metabolic pathway analysis was performed using Metaboanalyst 5.0. All p-values were adjusted for multiple testing (false-discovery rate, FDR p &lt; 0.20 considered significant). Results: The study population comprised 170 CRC patients (66 yoCRC and 104 aoCRC) and 49 healthy controls (34 young and 15 old). Association analyses revealed four differentially abundant metabolites: citrate (FDR p = 0.04), cholesterol (0.14), and two unidentified metabolites (UM). Metabolic pathways significantly altered in yoCRC vs. aoCRC included: carbohydrate metabolism (citrate cycle, FDR p = 0.04), carbohydrate biosynthesis (glyoxylate and dicarboxylate metabolism, FDR p = 0.004), amino-acid metabolism (alanine, aspartate, and glutamate metabolism, FDR p = 0.01, arginine biosynthesis, FDR p = 0.02, and amino-acid t-RNA biosynthesis, FDR p = 0.03). There were no significant metabolomic differences between young and old controls. Significant associations on survival analysis included: adipic acid with aoCRC (HR = 3.1, 95% CI = , 1.7-5.6, FDR p = 0.13, unadjusted analysis) suggesting worse survival with higher levels and 4-hydroxyhippuric acid with the whole cohort (HR = 0.4, 95% CI = 0.3-0.7, FDR p = 0.05, adjusted analyses) indicating better survival with higher levels. Conclusions: We identified significant differences in the citrate cycle - a core pathway of cellular metabolism associated with colorectal cancer. Metabolomic differences in pathways of carcinogenic significance (aspartate) and environmental exposures (arginine and dietary red meat) were also noted, suggesting potential relationships with younger age of CRC onset. [Table: see text]

Exploring demographic differences and outcomes in young-onset colorectal cancer.

35 Background: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States (1). The incidence of young-onset CRC is on the rise based on recent data (2). Previous research on other cancers has shown that patients living in rural areas have worse outcomes (3). This study aimed to investigate the geographic and socio-demographic disparities in young-onset CRC patients. Methods: We conducted a retrospective study on colorectal cancer patients between 1975 and 2016 using the Surveillance, Epidemiology, and End Results (SEER) database. Both univariate and multivariable analyses were performed to evaluate overall survival (OS) and disease-specific survival (DSS). Socio-demographic factors, including the location of residence [metro area (MA) or rural area (RA)], gender, race, insurance status, and marital status, were analyzed. Young-onset colorectal cancer (CRC) was defined as the age of diagnosis less than 50 years. The program used for analysis was SAS software 9.4 (SAS Institute Inc., Cary, NC, USA.) Univariate and multivariable models were analyzed using Cox proportional models. Demographic differences between urban and rural population were assessed using Wilcoxon Rank Sum test (continuous variable) and Chi-square test (categorical variables). Results: A total of 73,378 [RA, N = 7,636(10.6%); MA, N = 64,605(89.4%)] young-onset CRC patients were included. RA had more Caucasian patients compared to MA (80.5% vs 60%, p &lt; 0.001). Patients living in RA were more likely to be uninsured (4.8% vs 3%, p &lt; 0.001) than MA. During the study period, the incidence and mortality rates were consistently higher in RA vs. MA. Univariate and multivariable analysis showed that RA had worse OS (multivariate HR = 1.14; p &lt; 0.01) and DSS (multivariate HR = 1.15; p &lt; 0.001) compared to MA. Similarly, males, single and uninsured patients had worse OS and DSS compared to females, married, and insured patients, respectively. Conclusions: Our study identified social and demographic disparities in young-onset CRC incidence and outcomes. Potential causes may include access to healthcare, diet, health behavior, and environmental factors. Future research is needed to understand and attenuate such disparities.

Metabolomic differences in young-onset versus average-onset colorectal adenocarcinoma.

174 Background: Novel deleterious effects of environmental exposures may play a role in the rising incidence of young-onset colorectal cancer (yoCRC). We used metabolomics to assess differences between yoCRC and average-onset CRC (aoCRC), in comparison to healthy controls, which may suggest certain exposure risks. Methods: Patients with stage I-IV CRC and healthy controls were identified from prospective biobanks and categorized based on age&lt;50 years (yoCRC or young controls) or age&gt;60 years (aoCRC or older controls). Serum metabolites were profiled using GC-TOF mass spectrometry. Differential abundance of metabolites was investigated using unadjusted logistic regression. Metabolic pathway analysis was performed using Metaboanalyst 5.0. All p-values were adjusted for multiple testing (false-discovery rate, FDR p&lt;0.20 considered significant). Results: The study population comprised 170 CRC patients (66 yoCRC and 104 aoCRC) and 49 healthy controls (34 young and 15 old). Association analyses revealed four differentially abundant metabolites: citrate (FDR p=0.04), cholesterol (0.14), and two unidentified metabolites (UM). Metabolic pathways significantly altered in yoCRC vs. aoCRC included: carbohydrate metabolism (citrate cycle, FDR p=0.11), carbohydrate biosynthesis (glyoxylate and dicarboxylate metabolism, FDR p=0.03), amino-acid metabolism (alanine, aspartate, and glutamate metabolism, FDR p=0.04, arginine biosynthesis, FDR p=0.04, and amino-acid t-RNA biosynthesis, FDR p=0.04). There were no significant metabolomic differences between young and older controls. Conclusions: We identified significant differences in the citrate cycle - a core pathway of cellular metabolism and associated with colorectal cancer. Metabolomic differences in pathways of carcinogenic significance (aspartate) and environmental exposures (arginine and dietary red meat) were also noted, suggesting potential relationships with younger age of CRC onset. The study provides future directions for more precise analyses with a larger sample size for healthy controls and adjusting for confounders. [Table: see text]

Updated epidemiology of gastrointestinal cancers in East Asia.

Globally, gastrointestinal cancers represent more than one-fourth of all cancer incidence and one-third of cancer-related mortality. Although there has been much progress in screening colorectal cancer, the prognosis of other gastrointestinal cancers tends to be poor. The highest burden of gastrointestinal cancers, including stomach, liver, oesophageal and gallbladder cancers, was observed in regions in East Asia. The increasing burden of gastrointestinal cancers in East Asian regions is related to population growth, ageing and the westernization of lifestyle habits in this region. Furthermore, the rising incidence of young-onset colorectal cancer is an emerging trend in East Asia. This Review provides a comprehensive and updated summary of the epidemiology of gastrointestinal cancers in East Asia, with emphasis on comparing their epidemiology in East Asia with that in Western regions, and highlights the major risk factors and implications for prevention. Overall, to optimally reduce the disease burden incurred by gastrointestinal cancers in East Asian regions, a concerted effort will be needed to modify unhealthy lifestyles, promote vaccination against the hepatitis virus, control Helicobacter pylori, liver fluke and hepatitis virus infections, increase the uptake rate of colorectal cancer screening, enhance detection of early cancers and their precursors, and improve cancer survivorship through an organized rehabilitation programme.

S244 An Appraisal of the Referral, Uptake and Outcomes of Genetic Counseling and Testing in Patients With Young Onset Colorectal Cancer

Introduction: The incidence of young-onset colorectal cancer (YOCRC) defined as CRC in individuals < 50 years of age is rapidly rising. Germline genetic testing is currently recommended for all patients with CRC< 50 years. Germline pathogenic variants (PV) are detected in 16-20% of patients with YOCRC and many are diagnosed with an actionable PV not typically associated with CRC, highlighting a need for genetic counseling and multi-panel gene testing (MGPT) in these patients. We aimed to determine the rate of referral to genetic counseling, and uptake and outcomes of germline testing in YOCRC patients seen at a tertiary referral center. Methods: Patients diagnosed with YOCRC from 2010-2019 were included. Patients with appendiceal cancer, known family history of a hereditary cancer syndrome and inflammatory bowel disease were excluded. Demographic data including age, sex, race and family history of CRC were extracted from the electronic medical record (EMR).Genetic counseling referral was confirmed through an order in the EMR, clinical documentation in office visits with colorectal surgery, oncology or gastroenterology, or a completed visit with the genetic counselor. Data was analyzed using STATA, Chi-square and t-test and descriptive analyses were included. Results: 793 YOCRC patients (457 male and 336 female) were included. 56% (445) were referred for genetic counseling and 88% of referred patients completed genetic testing. 20.5% had a PV detected; 83% were in CRC associated genes and 18% were in other actionable genes (Table). Referral to genetic counseling was higher in younger patients (mean age= 40 years in those referred vs. mean age= 43 years in those not referred, p < 0.05) and those with a family history of CRC (70% of patients with family history of CRC vs. 53% of patients without family history were referred, p< 0.05) There was no significant association between referral rate and sex or race. Conclusion: Even in a large academic center, the rates of referrals for genetic counseling in patients with YOCRC were documented in only about half the patients. 1 in 5 YOCRC patients had a PV detected. If the 348 patients not referred to genetic counseling underwent testing, an additional 71 patients may be detected with a germline PV. Our findings highlight the need to raise awareness of the importance of genetic counseling and testing in YOCRC patients, and suggest that health systems should consider implementing care pathways to mitigate the potential impact of under-referral. Table 1. - Demographics, Referral to and Uptake of Genetic Counseling and Testing and Outcome of Genetic Testing Number of patients with YOCRC 793 Demographics N (%) Mean (SD) Age 41.9 (6.8) Sex Male 457 (57.6) Female 336 (42.4) Race White 684 (86.3) Black 72 (9.1) Other 37 (4.7) Family History of CRC Yes 280 (40.2) No 417 (59.8) Referral for Genetic Counseling 445 (56.1) Attended Genetic Counseling 390 (87.6) Underwent Genetic Testing 376 (96.4) • Pathogenic Variant Detected 77 (20.5) • Variant of Uncertain Significance Detected 88 (23.4) • No Variant Detected 211 (56.1) Genetic Testing Outcomes Genetic Syndrome Pathogenic Variant Number of Patients Total (%) CRC and polyposis genes N=64 (83%) Lynch syndrome N=37 (48%) MLH1 11 37 (48) MSH2 13 MSH6 8 PMS2 5 FAP N= 15 (19.4%) APC 15 15 (19.4) MYH- Associated polyposis N =10 (12.9%) MUTYH (Biallelic) 6 10 (12.9) MUTYH (Monoallelic) 4 Juvenile polyposis syndrome N = 1 (1.2%) SMAD4 1 1 (1.2) MSH3 (monoallelic) 1 1 (1.2) Other genes N=13 (17%) ATM 4 13 (17) BRCA1/2 4 BLM (monoallelic) 1 CHEK2 2 FLCN 1 CDKN2A 1

Direct medical costs of young-onset colorectal cancer: a worldwide systematic review

BackgroundGiven the rising incidence of young-onset colorectal cancer (yCRC) among individuals younger than 50 years old, understanding the economic burden of yCRC is required to inform the delivery of healthcare services. Therefore, we conducted a systematic review of studies assessing the direct medical costs of yCRC, and where relevant average-age onset CRC (aCRC).MethodsWe searched MEDLINE, EMBASE, and Web of Science from inception to May 2022 for original, peer-reviewed studies, that reported direct medical costs (e.g., chemotherapy, radiotherapy, outpatient visits, inpatient care, prescription medications) for yCRC and aCRC. We used a modified version of the Consolidated Health Economic Evaluation Reporting Standards checklist to appraise the studies. Costs were inflation-adjusted to 2020 US dollars.ResultsWe included 14 studies from 10 countries, including the USA, England, France, Korea, Vietnam, China, Italy, Australia, Canada and Japan. Five studies focused on prevalent disease and reported annualized per-capita cost of prevalent yCRC, ranging from $2,263 to $16,801 and $1,412 to $14,997 among yCRC and aCRC cases, respectively. Nine studies estimated the cost of incident disease. Synthesis of per-capita costs incurred 12 months following colorectal cancer diagnosis ranged from $23,368 to $89,945 for yCRC and $19,929 to $67,195 for aCRC. Five studies used multivariable approaches to compare costs associated with yCRC and aCRC, four showed no differences and one suggested greater costs with yCRC.ConclusionOur synthesis of direct medical costs of yCRC across multiple jurisdictions provide relevant information for healthcare decisions, including on-going considerations for expanding CRC screening strategies to younger adults.

Metagenomic analysis of the fecal microbiome in patients with colorectal cancer compared to healthy controls as a function of age.

3532 Background: Colorectal cancer (CRC) incidence is increasing in young patients ( &lt; 50 years old) without a clear etiology. Emerging data has implicated the fecal microbiome in CRC carcinogenesis. However, its impact on young onset CRC (YO-CRC) is poorly defined. Colibactin producing E. Coli and fadA producing Fusobacterium nucleatum can drive CRC carcinogenesis, however their effects across the age spectrum are unknown. Methods: We performed a meta-analysis of fecal metagenomics sequencing from n = 692 patients with CRC and n = 602 healthy controls from eleven studies to evaluate species and known microbial derived factors (colibactin and FadA) associated with CRC as a function of age. Generalized linear mixed effects regression was used to model the predicted prevalence of gene families and taxa as a non-linear function of age. Two-stage individual patient data meta-analysis (IPDMA) with adjustment for gender, CRC status, and body mass index was also used to estimate summary odds ratios for colibactin, F. nucleatum, and E. Coli. Interaction ORs were obtained to assess the difference in the effect of each gene or taxa on CRC case status in YO-CRC. Shannon Diversity index and metabolic pathway differences in the fecal metagenome for YO-CRC patients were assessed using phyloseq and MetaCyc respectively using an IPDMA approach. Results: Summary odds ratios (OR) for CRC were increased relative to controls with the presence of colibactin (OR 1.92 95%CI 1.08-3.38), fadA (OR 4.57 95%CI 1.63-12.85), and F. nucleatum (OR 6.93 95%CI 3.01-15.96) in models of all patients adjusted for age, gender, and body mass index. The OR for CRC for the presence of E.coli was 2.02 (0.92-4.45). An increase in the prevalence of F. nucleatum (OR = 1.40 [1.18; 1.65] and Escherichia coli (OR = 1.14 [1.02; 1.28]) per 10-year increase in age was observed in models including samples from both CRC and healthy controls. No difference was observed for Shannon Diversity (OR 1.36 95%CI 0.68-2.72) or MetaCyc pathways in YO-CRC patients. Species relative abundance was differentially enriched in YO-CRC relative to old CRC patients and controls for five species- Intestinimonas butyriciproducens, Holdemania filiformis, Firimicutues bacterium CAG 83, Bilophilia wadsworthia, and Alistipes putredinis. Conclusions: Strong associations with CRC status were observed for colibactin, fadA, and F. nucleatum with increased F. nucleatum in older patients. Several species were enriched in YO-CRC patients including B. wadsworthia which can produce carcinogenic sulfur metabolites and is increased with adherence to a sulfur microbial diet-low in vegetables and legumes. A sulfur microbial diet has also been associated with higher incidence of YO-CRC in population studies (Nguyen Gastroenterology 2021). Additional study is warranted to understand causal mechanisms of enriched species observed in YO-CRC patients.

Risk of Anxiety and Depression after Diagnosis of Young-Onset Colorectal Cancer: A Population-Based Cohort Study.

Given the increasing incidence of young-onset colorectal cancer (yCRC; <50 years), we aimed to evaluate the risk of depression and anxiety in individuals with yCRC in comparison to average-age-onset CRC (aCRC; ≥50 years) and to cancer-free controls, with stratification by sex. Our cohort study identified individuals (≥18 years) with CRC and cancer-free controls (10:1) matched on age and sex using population-based linked administrative health databases in British Columbia, Canada. We assessed depression and anxiety using validated algorithms. We evaluated the risk of depression and anxiety using multivariable Cox proportional hazard models. The cohort included 54,634 individuals with CRC (46.5% female, mean age 67.9 years) and 546,340 controls (46.5% female, mean age 67.9 years). Those with yCRC as compared to aCRC had an increased risk for depression (adjusted hazard ratio [aHR] 1.41; 95% confidence interval [CI] 1.25 to 1.60), and when stratified by sex, the risk was only significant among males (aHR 1.76; 95% CI 1.48 to 2.10). When comparing individuals with yCRC to cancer-free controls, the overall risk of depression (aHR 1.00; 95% CI 0.92 to 1.10) and anxiety (aHR 1.10; 95% CI 0.95 to 1.27) was non-significant; however, males had a significantly higher risk for mental health disorders, specifically depression (aHR 1.17; 95% CI 1.03 to 1.33). Altogether, our findings that individuals with yCRC experience higher risk of depression compared to those with aCRC as well as cancer-free controls, particularly among males, suggest effects of age and sex on mental health outcomes.

Comparison of comprehensive genomic profiles between young-onset and average-onset colorectal cancer.

167 Retraction The abstract by Torrejon et al entitled, “Comparison of comprehensive genomic profiles between young-onset and average-onset colorectal cancer.,” ( Journal of Clinical Oncology 40, no. 4, suppl 167) published on January 19, 2022, has been retracted due to calculation errors. Current age was used for the analysis instead of age at diagnosis. This error significantly changed the results and conclusion of the abstract. Background: The incidence of young-onset colorectal cancer (yoCRC) is rising for unknown reasons. This study assessed for differences in comprehensive genomic profiles between yoCRC and average-onset colorectal cancer (aoCRC). Methods: All patients with CRC seen at Cleveland Clinic that had tumor-based next generation sequencing (NGS) performed as part of their care with a clinically available assay between January 2017 and September 2020 were included. The cohort was divided based on age of diagnosis, with yoCRC defined as age of CRC diagnosis &lt;50 years old. All clinical data and genomic alterations were included for analysis. We assessed for differences in clinical data and NGS findings between yoCRC and aoCRC using Fisher’s exact test, adjusted for primary tumor sidedness. Overall survival (OS) by genomic alteration was estimated by Kaplan-Meier methods and compared using log rank test. Results: The study population comprised of 51 yoCRC patients and 211 aoCRC patients. There were no significant differences in sex, race or ethnicity between yoCRC and aoCRC patients. Compared to aoCRC patients, yoCRC patients were more likely to present at diagnosis with stage IV disease (81% vs. 56%, p = 0.02) and have left-sided primary tumors (69% vs. 60%, p = 0.26). YoCRC tumors were more likely to have mutations in APC, KRAS, TP53 and FLT3 compared to aoCRC tumors, independent of tumor sidedness. These data are summarized in Table. Compared to left-sided tumors, right-sided tumors had significantly higher frequency of KRAS (67.7% vs. 48.8%, p = 0.003), BRAF (15.2% vs. 3.1%, p = 0.0006) and PTEN (16.2% vs. 3.1%, p value = 0.0003) alterations. AoCRC patients had significantly longer OS compared to yoCRC patients (median OS: 70.0 months vs. 36.3 months, p=0.004). Black (37.2 months, n=35) and Asian (37.8 months, n=7) patients had significantly worse median OS compared to White patients (67.8 months, n=199), p-value 0.005. In the overall population, patients with APC mutations had significantly better OS compared to those with APC wildtype tumors (median OS: 92.6 months vs. 54.4 months, p=0.001). Patients with FLT3 mutations had worse median OS compared to those with FLT3 wildtype tumors (median OS: 42.0 months vs. 64.8 months, p=0.007). There were no survival differences based on MSI status. Conclusions: In this series, yoCRC patients were more likely to present with stage IV disease and experienced worse OS compared to aoCRC patients. YoCRC patients were more likely to have mutations in APC, KRAS, TP53 and FLT3, independent of tumor sidedness. Mutations in FLT3 correlated with worse OS.[Table: see text]

Racism Is a Modifiable Risk Factor: Relationships Among Race, Ethnicity, and Colorectal Cancer Outcomes

Racism Is a Modifiable Risk Factor: Relationships Among Race, Ethnicity, and Colorectal Cancer Outcomes

Survival in Young-Onset Metastatic Colorectal Cancer: Findings From Cancer and Leukemia Group B (Alliance)/SWOG 80405.

The incidence of young-onset colorectal cancer (yoCRC) is increasing. It is unknown if there are survival differences between young and older patients with metastatic colorectal cancer (mCRC). We studied the association of age with survival in 2326 mCRC patients enrolled in the Cancer and Leukemia Group B and SWOG 80405 trial, a multicenter, randomized trial of first-line chemotherapy plus biologics. The primary and secondary outcomes of this study were overall survival (OS) and progression-free survival (PFS), respectively, which were assessed by Kaplan-Meier method and compared among younger vs older patients with the log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated based on Cox proportional hazards modeling, adjusting for known prognostic variables. All statistical tests were 2-sided. Of 2326 eligible subjects, 514 (22.1%) were younger than age 50 years at study entry (yoCRC cohort). The median age of yoCRC patients was 44.3 vs 62.5 years in patients aged 50 years and older. There was no statistically significant difference in OS between yoCRC vs older-onset patients (median = 27.07 vs 26.12 months; adjusted HR = 0.98, 95% CI = 0.88 to 1.10; P = .78). The median PFS was also similar in yoCRC vs older patients (10.87 vs 10.55 months) with an adjusted hazard ratio of 1.02 (95% CI = 0.92 to 1.13; P = .67). Patients younger than age 35 years had the shortest OS with median OS of 21.95 vs 26.12 months in older-onset patients with an adjusted hazard ratio of 1.08 (95% CI = 0.81 to 1.44; Ptrend = .93). In this large study of mCRC patients, there were no statistically significant differences in survival between patients with yoCRC and CRC patients aged 50 years and older.

Young-onset colorectal cancer: A review.

Despite the general decrease in overall incidence of colorectal cancer since the early 1990s, the incidence of colorectal cancer in patients less than 50 years old has nearly doubled. A systematic review was performed using the PubMed database (2011-2020) and Cochrane Database of Systematic Reviews (2011-2021) to identify studies (published in English) evaluating epidemiologic, clinical, hereditary, and molecular features; as well as evaluation, management, and prognosis of young-onset colorectal cancer patients. Our search yielded a total of 3401 articles, after applying our inclusion criteria. We fully reviewed 94 full-length studies. This systematic review demonstrates the increasing incidence of young-onset colorectal cancer and highlights the importance of being hypervigilant for the differential diagnosis colorectal cancer when evaluating a young adult who presents with gastrointestinal symptoms.

Trends in the Incidence of Young-Onset Colorectal Cancer With a Focus on Years Approaching Screening Age: A Population-Based Longitudinal Study.

BackgroundWith recent evidence for the increasing risk of young-onset colorectal cancer (yCRC), we had the objective to evaluate the incidence of yCRC in 1-year age increments, particularly focusing around the screening age of 50 years.MethodsWe conducted a longitudinal study using linked administrative health databases in British Columbia, Canada, including a provincial cancer registry, inpatient and outpatient visits, and vital statistics from January 1, 1986, to December 31, 2016. We calculated incidence rates per 100 000 at every age from 20 to 60 years and estimated annual percent change in incidence (APCi) of yCRC using joinpoint regression analysis.ResultsWe identified 3614 individuals with yCRC (49.9% women). The incidence of CRC steadily increased from 20 to 60 years, with a marked increase from 49 to 50 years (incidence rate ratio = 1.19, 95% confidence interval [CI] = 1.04 to 1.34). Furthermore, there was a trend of increased incidence of yCRC among women (APCi = 0.79%, 95% CI = 0.22% to 1.36%) and men (APCi = 2.17%, 95% CI = 1.59% to 2.76%). Analyses stratified by age yielded APCis of 2.49% (95% CI = 1.36% to 3.63%) and 0.12% (95% CI = −0.54% to 0.79%) for women aged 30-39 years and 40-49 years, respectively, and 2.97% (95% CI = 1.65% to 4.31%) and 1.86% (95% CI = 1.19% to 2.53%) for men.ConclusionsOur findings indicate a steady increase over 1-year age increments in the risk of yCRC during the years approaching and beyond screening age. These findings highlight the need to raise awareness as well as continue discussions regarding considerations of lowering the screening age.

Trends and Clinical Outcomes in Young-onset Colorectal Cancer Patients

Young individuals with colorectal cancer (CRC) tend to be diagnosed at advanced stages and are not routinely included in screening programmes. This study describes the incidence, disease pattern and factors affecting overall survival in young-onset CRC. A retrospective study of young-onset CRC patients diagnosed between 2010 and 2017 in a tertiary hospital was conducted. There were 99 patients, 69.7% had left-sided while 30.3% had right-sided CRC. The mean age was 43.3 years (43.3±5.0) and 62 patients (62.6%) were male. The incidence of young-onset CRC has been on the rise since 2014. Out of 99 patients, 65 (65.7%) underwent elective surgery, 30 (30.3%) underwent emergency surgery and the remainder 5 (4.0%) were palliated. The most common presenting complaints for patients who underwent elective surgery were abdominal pain, per-rectal bleeding and altered bowel habits. For patients who required emergency surgery, 20 (66.6%) presented with intestinal obstruction and 10 (33.3%) had intestinal perforation. There were 42 (42.4%) stage III CRC and 20 (20.2%) stage IV CRC. The most frequent metastatic site was the liver (20/20, 100%). Five patients had signet ring cells (5.1%) in their histology while 15 (15.2%) had mucinous features. The overall 5-year survival of young-onset CRC was 82.0%. Advanced overall stage (hazard ratio (HR) 6.1, CI 1.03-3.62) and signet ring histology (HR 34.2, CI 2.24-5.23) were associated with poor prognosis. Young-onset CRC tend to be left-sided with advanced presentations. However, their 5-year survival remains favourable as compared to the general population.