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Colorectal cancer (CRC) still constitutes a significant healthcare burden. Although its overall incidence is reducing, the incidence of early-onset CRC is increasing. There is uncertainty about the association between CRC and BRCA2 mutations and also, even though most cancers metastasize to the liver, acute liver failure (ALF) from metastatic cancer and specifically CRC is uncommon. This is a case of a young patient with BRCA2 mutation who presented with a large obstructing CRC with extensive metastatic burden to the liver, causing a fatal ALF. This case shows the growing number of ALFs associated with metastatic disease and suggests a possible association between BRCA2 mutation and CRC. This association needs more research to establish.

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Background: Colorectal cancer (CRC) screening has been shown to be effective and cost-saving. However, the trend of rising incidence of early-onset CRC challenges the current national screening program solely for people ≥50 years in Germany, where extending the screening to those 45-49 years might be justified. This study aims to evaluate the cost-effectiveness of CRC screening strategies starting at 45 years in Germany. Method: DECAS, an individual-level simulation model accounting for both adenoma and serrated pathways of CRC development and validated with German CRC epidemiology and screening effects, was used for the cost-effectiveness analysis. Four CRC screening strategies starting at age 45, including 10-yearly colonoscopy (COL), annual/biennial fecal immunochemical test (FIT), or the combination of the two, were compared with the current screening offer starting at age 50 years in Germany. Three adherence scenarios were considered: perfect adherence, current adherence, and high screening adherence. For each strategy, a cohort of 100,000 individuals with average CRC risk was simulated from age 20 until 90 or death. Outcomes included CRC cases averted, prevented death, quality-adjusted life-years gained (QALYG), and total incremental costs considering both CRC treatment and screening costs. A 3% discount rate was applied and costs were in 2023 Euro. Result: Initiating 10-yearly colonoscopy-only or combined FIT + COL strategies at age 45 resulted in incremental gains of 7-28 QALYs with incremental costs of €28,360-€71,759 per 1,000 individuals, compared to the current strategy. The ICER varied from €1,029 to €9,763 per QALYG, and the additional number needed for colonoscopy ranged from 129 to 885 per 1,000 individuals. Among the alternatives, a three times colonoscopy strategy starting at 45 years of age proves to be the most effective, while the FIT-only strategy was dominated by the currently implemented strategy. The findings remained consistent across probabilistic sensitivity analyses. Conclusion: The cost-effectiveness findings support initiating CRC screening at age 45 with either colonoscopy alone or combined with FIT, demonstrating substantial gains in quality-adjusted life-years with a modest increase in costs. Our findings emphasize the importance of implementing CRC screening 5 years earlier than the current practice to achieve more significant health and economic benefits.

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PURPOSE: Colorectal cancer (CRC) screening has been implemented in Tianjin, China since 2012. The objective was to estimate the neoplasia detection rate in a high-risk population by age and sex and to investigate the potential factors associated with colorectal neoplasia. PATIENTS AND METHODS: This study is based on data of the Tianjin CRC screening program from 2012 to 2020. Residents with a positive high-risk factors questionnaire (HRFQ) or a positive faecal immunochemical test (FIT) were identified as high-risk participants and were subsequently recommended for a free colonoscopy. RESULTS: A total of 4,117,897 eligible participants aged 40-74 years completed both a HRFQ and FIT, and 217,164 (5.3%) of them were identified as high-risk participants. Positive rates of preliminary screening increased with age and were higher in females than in males. For 57,971 participants undertaking colonoscopy, the detection rates of nonadvanced adenoma, advanced adenoma and CRC were 37.8%, 5.7% and 1.6%, respectively. Detection rates of advanced neoplasia increased from the age of 50 and were higher in males. For nonadvanced neoplasia, a strong increase was observed in males from the age of 40 and in females from the age of 50. Male sex had a greater impact on individuals aged 40-49 than on older individuals. Several factors including current smoking, drinking, and higher body mass index (BMI) were significantly associated with the presence of neoplasia, whereas, these associations were mainly restricted to individuals aged above 50 but not those aged 40-49 years. CONCLUSIONS: These findings support that age-specific risk stratification and sex-specific initiating ages for CRC screening should be recommended to improve the accuracy and effectiveness of current screening strategy.

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PURPOSE: Metastatic early-onset colorectal cancer (EO-CRC) is on the rise, yet there is a dearth of predictive models for this disease. Therefore, it is crucial to develop a nomogram to aid in the early detection and management of metastatic colorectal cancer in young patients. METHODS: We retrieved data from the SEER database on patients with metastatic colorectal cancer aged 50 or younger between 2010 and 2017. The data were randomly allocated in a 7:3 ratio to training and validation cohorts, and univariate and multivariate Cox regression analyses were used to identify independent prognostic factors for overall survival (OS) and cancer-specific survival (CSS) at 1, 3, and 5 years. The nomograms were developed based on these factors, and their discriminatory and calibration capabilities were validated. Using the nomogram risk scores, patients were stratified into low-risk and high-risk groups. RESULTS: The study included 2470 patients with metastatic EO-CRC. Univariate and multivariate Cox regression analysis identified 12 independent risk factors that were included in the nomogram. The training cohort had a consistency index (C-index) of 0.71, while the validation cohort had a C-index of 0.70, demonstrating good predictive accuracy. Calibration plots showed a high level of consistency between the observed and predicted values, with overlapping plots along the diagonal. The decision curve analysis (DCA) revealed that the nomogram had a high clinical application value. CONCLUSIONS: The novel nomograms were created to predict the prognosis of patients with metastatic EO-CRC, which can aid clinicians in developing more effective treatment strategies and contribute to more accurate prognostic assessments.

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BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC; patients < 50 years old) has been rising rapidly, whereas the EOCRC genetic susceptibility remains incompletely investigated. Here, we aimed to systematically identify specific susceptible genetic variants for EOCRC. METHODS: Two parallel GWASs were conducted in 17,789 CRC cases (including 1490 EOCRC cases) and 19,951 healthy controls. A polygenic risk score (PRS) model was built based on identified EOCRC-specific susceptibility variants by using the UK Biobank cohort. We also interpreted the potential biological mechanisms of the prioritized risk variant. RESULTS: We identified 49 independent susceptibility loci that were significantly associated with the susceptibility to EOCRC and the diagnosed age of CRC (both P < 5.0×10-4), replicating 3 previous CRC GWAS loci. There are 88 assigned susceptibility genes involved in chromatin assembly and DNA replication pathways, mainly associating with precancerous polyps. Additionally, we assessed the genetic effect of the identified variants by developing a PRS model. Compared to the individuals in the low genetic risk group, the individuals in the high genetic risk group have increased EOCRC risk, and these results were replicated in the UKB cohort with a 1.63-fold risk (95% CI: 1.32-2.02, P = 7.67×10-6). The addition of the identified EOCRC risk loci significantly increased the prediction accuracy of the PRS model, compared to the PRS model derived from the previous GWAS-identified loci. Mechanistically, we also elucidated that rs12794623 may contribute to the early stage of CRC carcinogenesis via allele-specific regulating the expression of POLA2. CONCLUSIONS: These findings will broaden the understanding of the etiology of EOCRC and may facilitate the early screening and individualized prevention.

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PURPOSE: The incidence of colorectal cancer (CRC) is rising in people under age 50 (early-onset). Early-onset survivors face CRC during a critical point in their lives; many are establishing their families and careers. We sought to identify the unmet needs in a sample of early-onset CRC survivors and the resources they desired to address those needs. METHODS: We conducted a mixed methods study where participants completed the Cancer Survivors Unmet Needs (CaSUN) survey and a subsequent qualitative interview to expand on their unmet needs and desired resources. RESULTS: A total of 12 CRC survivors participated and 83% identified at least one unmet need, with an average of 13 unmet needs reported. Unmet needs were identified across every domain of the CaSUN measure, most commonly in the existential survivorship domain. Qualitative results demonstrated that survivors need more resources tailored for people their age and additional support for their families, including young children. CONCLUSION: Early-onset CRC survivors' needs are framed by the stage of their lives in which they are diagnosed, and the demand for interventions to support these survivors will continue to rise. The results of this study can inform future, tailored interventions for early-onset CRC survivors with substantial needs.

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There is an increase in the incidence of early onset colorectal carcinoma (EOCRC). To better understand if there is any difference in molecular pathogenesis of EOCRC and late onset colorectal carcinoma (LOCRC), we compared the clinical, histological, transcriptome, and methylome profile of paired CRC and healthy colonic tissue from 67 EOCRC and 98 LOCRC patients. The frequency of stage 3 CRC, lymph node involvement, lymphovascular invasion, and perineural invasion was higher in the EOCRC group. Many of the cancer related pathways were differentially expressed in CRC tissue in both EOCRC and LOCRC patients. However, the magnitude of differential expression for some groups of genes, such as DNA damage repair genes and replication stress genes, were significantly less pronounced in the EOCRC group, suggesting less efficient DNA damage repair to be associated with EOCRC. A more marked methylation of "growth factor receptor" genes in LOCRC correlated with a more pronounced down-regulation of those genes in that group. From a therapeutic point of view, more over-expression of fatty acid synthase (FASN) among the LOCRC patients may suggest a better response of FASN targeted therapy in that group. The age of onset of CRC did not appear to modify the response of cis-platin or certain immune checkpoint inhibitors. We found some differences in the molecular pathogenesis in EOCRC and LOCRC that may have some biological and therapeutic significance.

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BACKGROUND: The incidence rate of colorectal cancer (CRC) is increasing among patients below 50 years of age. The reason for this is unclear, but could have to do with the fact that indicative variables, such as tumour location, gender preference and genetic preponderance have not been followed up in a consistent mann er. The current study was primarily conducted to improve the hereditary CRC screening programme by assessing the demographic and clinicopathological characteristics of early-onset CRC compared to late-onset CRC in northeast Iran. METHODS: This retrospective study, carried out over a three-year follow-up period (2014-2017), included 562 consecutive CRCs diagnosed in three Mashhad city hospital laboratories in north-eastern Iran. We applied comparative analysis of pathological and hereditary features together with information on the presence of mismatch repair (MMR) gene deficiency with respect to recovery versus mortality. Patients with mutations resulting in absence of the MMR gene MLH1 protein product and normal BRAF status were considered to be at high risk of Lynch syndrome (LS). Analyses using R studio software were performed on early-onset CRC (n = 222) and late-onset CRC (n = 340), corresponding to patients ≤50 years of age and patients > 50 years. RESULTS: From an age-of-onset point of view, the distribution between the genders differed with females showing a higher proportion of early-onset CRC than men (56% vs. 44%), while the late-onset CRC disparity was less pronounced (48% vs. 52%). The mean age of all participants was 55.6 ± 14.8 years, with 40.3 ± 7.3 years for early-onset CRC and 65.1 ± 9.3 years for late-onset CRC. With respect to anatomical tumour location (distal, rectal and proximal), the frequencies were 61, 28 and 11%, respectively, but the variation did not reach statistical significance. However, there was a dramatic difference with regard to the history of CRC in second-degree relatives between two age categories, with much higher numbers of family-related CRCs in the early-onset group. Expression of the MLH1 and PMS2 genes were significantly different between recovered and deceased, while this finding was not observed with regard to the MSH6 and the MSH2 genes. Mortality was significantly higher in those at high risk of LS. CONCLUSION: The variation of demographic, pathological and genetic characteristics between early-onset and late-onset CRC emphasizes the need for a well-defined algorithm to identify high-risk patients.

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Background: Colorectal cancer (CRC) incidence is rising worldwide, as well as in the Republic of Kazakhstan, while its occurrence is also increasing in the younger population. Hereditary forms associated with the development of colon and rectal cancer and early-onset CRC have never been studied in the population of Kazakhstan. The aim of this research was to investigate the spectrum of CRC-related gene mutations to determine which mutations cause early onset of CRC in the Kazakhstan population. Methods: The study included 125 unrelated patients from Kazakhstan (range 17-50 years in age) with early onset CRC. Genomic DNA was obtained from peripheral blood of the patients. Next-generation sequencing was performed using the TruSightCancer Kit on the MiSeq platform. The Studio Variant was used to annotate and interpret genetic variants. Results: Bioinformatics analysis of Next-generation sequencing data revealed 11,152 variants from 85 genes, of them, 3,790 missense, 6,254 synonymous variants, 44 3'UTR variants, 10 frameshift variants, five stop-gain variants, four in-frame deletions, two splice donors, one splice acceptor variant, and 1,042 intron or non-coding variants. APC, BRCA2/1, ALK, BRIP1, EGFR, FANCA, FANCD2, FANCI, HNF1A, MEN1, NSD1, PMS2, RECQL4, RET, SLX4, WRN, and XPC genes mutated most often. According to the ACMG guidelines and LOVD/ClinVar databases, 24 variants were pathogenic (10 frameshifts, five missenses, five stop-gain, one in-frame deletion, and three splice-site mutations), and 289 were VUS with population frequency <1%, 131 of them were attributed as deleterious. In the study, 50% of all pathogenic mutations found in Kazakhstani patients with early CRC onset were identified in the subgroups with a family history of CRC and primary multiple tumors. In APC, pathogenic mutations were most often (21%). Conclusion: Pathogenic and likely pathogenic mutations were found in 20 (16%) out of 125 patients. Eight novel pathogenic mutations detected in FANCI, APC, BMPR1, ATM, and DICER1 genes have not been reported in previous literature. Given the high frequency and wide spectrum of mutations, NGS analysis must be carried out in families with a history of CRC/CRC-related cancers with the purpose to identify cause-effective mutations, clarify the clinical diagnosis, and prevent the development of the disease in other family members.

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BACKGROUND: Racial disparities in incidence of colorectal cancer (CRC) exist. In Hispanics, CRC was the second most commonly diagnosed cancer in 2012. METHODS: We abstracted the national estimates for Hispanics/Whites with CRC using the SEER database between 2000 and 2010. Trends in incidence, mortality, gender and stage of disease were analyzed for early-onset (age<50; EO - young) and late-onset (age>50; LO - old) cases. RESULTS: The overall incidence of CRC increased by 48% in Hispanics. 38% increase in incidence of LO CRC and 80% increase in incidence of EO CRC was seen in this ethnic group. Hispanics and Whites showed higher percentage of distant tumors for both age groups. There was no deviation in overall trend between males and females. CONCLUSIONS: Although there is an overall decrease in incidence of CRC in Whites increase was seen in Hispanics. While incidence of EO CRC is increasing in both races, LO CRC incidence is increasing in Hispanics not in Whites. This data suggest that disparities in incidence of EO and LO CRC exist between Hispanics and Whites.

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AIM: The study aimed to assess whether there has been an increase in the incidence of colorectal cancer (CRC) among young patients in Victoria and whether such cancers are more advanced at presentation. METHOD: The Victorian Cancer registry database was searched for patients, 18-50 years of age, diagnosed with CRC [young colorectal cancer (YCRC)] between 2000 and 2010. Average annual percentage changes and incidence rate ratios (IRRs) were calculated to characterize trends in CRC rates over time and to make comparisons with patients over 50 years of age with CRC [late colorectal cancer (LCRC)]. RESULTS: Of 37432 CRCs registered during the study period, 2635 (7%) were in YCRC patients (annual increase in incidence = 1.7%; 95% CI: 0.5-2.9), compared with 34797 (93%) in LCRC patients (annual increase in incidence = 1.3%; 95% CI: 0.9-1.6). A small, nonsignificant increase in the incidence of YCRC over time was observed [IRR = 1.004 (95% CI: 0.992-1.016) for YCRC vs. 0.989 (95% CI: 0.986-0.992) for LCRC]. Rectal cancer was more common in YCRC patients than in LCRC patients (42% vs. 34%, respectively; P < 0.0001). The cancer would have been seen on flexible sigmoidoscopy in 63% of YCRC patients compared with 53.6% of LCRC patients (P < 0.0001). YCRC patients were more likely to have node-positive disease (49.3% YCRC patients vs. 40% LCRC patients; P < 0.0001), especially those with colonic cancer (52.7% YCRC patients vs. 41.2% LCRC patients; P < 0.0001). CONCLUSION: There has been an increase in incident cases of YCRC. A small, nonsignificant increase in the incidence of YCRC over time was observed. Young patients are more likely to have rectal cancer and to be node positive.

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