A High Percentage of Early-age Onset Colorectal Cancer Is Potentially Preventable.
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ABSTRACT:
SUBMITTER: Stanich PP
PROVIDER: S-EPMC8083989 | biostudies-literature | 2021 Apr
REPOSITORIES: biostudies-literature
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A High Percentage of Early-age Onset Colorectal Cancer Is Potentially Preventable.
Stanich Peter P PP Pelstring Keith R KR Hampel Heather H Pearlman Rachel R
Gastroenterology 20201211 5
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Project description:To identify the gene expression of early-onset colorectal cancer, we sampled early-onset colorectal cancer patients (age < 50) and late-onset colorectal cancer paitients (age > 70) We then performed gene expression profiling analysis using data obtained from RNA-seq of early-onset colorectal cancer tissues and late-onset colorectal cancer tissues.
2023-02-08 | GSE213092 | GEO
Project description:Early onset colorectal cancer tissues and late onset colorectal cancer tissues
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Project description:Background & aimsColorectal cancer (CRC) incidence and mortality are increasing among persons younger than 50 years old in the United States, but risk factors associated with early-onset CRC (EOCRC) have not been widely studied.MethodsWe conducted a case-control study of US veterans 18 to 49 years old who underwent colonoscopy examinations from 1999 through 2014. EOCRC cases were identified from a national cancer registry; veterans who were free of CRC at their baseline colonoscopy through 3 years of follow-up were identified as controls. We collected data on age, sex, race/ethnicity, body weight, body mass index (BMI), diabetes, smoking status, and aspirin use. Multivariate-adjusted EOCRC odds were estimated for each factor, with corresponding 95% confidence interval (CI) values.ResultsOur final analysis included 651 EOCRC cases and 67,416 controls. Median age was 45.3 years, and 82.3% were male. Higher proportions of cases were older, male, current smokers, nonaspirin users, and had lower BMIs, compared with controls (P < .05). In adjusted analyses, increasing age and male sex were significantly associated with increased risk of EOCRC, whereas aspirin use and being overweight or obese (relative to normal BMI) were significantly associated with decreased odds of EOCRC. In post hoc analyses, weight loss of 5 kg or more within the 5-year period preceding colonoscopy was associated with higher odds of EOCRC (odds ratio 2.23; 95% CI 1.76-2.83).ConclusionsIn a case-control study of veterans, we found increasing age and male sex to be significantly associated with increased risk of EOCRC, and aspirin use to be significantly associated with decreased risk; these factors also affect risk for CRC onset after age 50. Weight loss may be an early clinical sign of EOCRC. More intense efforts are required to identify the factors that cause EOCRC and signs that can be used to identify individuals at highest risk.
| S-EPMC7343609 | biostudies-literature
Project description:BackgroundThe rising incidence of early onset colorectal cancer (EOCRC) might reflect a novel tumour entity.AimsTo evaluate clinicopathological characteristics of sporadic EOCRC (in patients < 50 years old) and investigate changes over time METHODS: All patients with sporadic EOCRC between 1989 and 2016 were included and divided by age: 20-29 years (group I), 30-39 years (group II) and 40-49 years (group III).ResultsWe included 6400 patients. The presence of signet-ring cells and more poorly differentiated tumours were more common in the younger age groups: 5.4% and 3.7% for signet-ring cells in group I and II vs 1.4% in group III (P < 0.01), and 28.5% and 20.3% for poorly differentiated in group I and II vs 16.6% in group III, (P < 0.01 group I; P = 0.07 group II). Positive lymph nodes were more frequently observed in the younger age groups: 16.2% in group I vs 9.3% in group II (P = 0.01) and 7.9% (P < 0.01) in group III. Over time, a greater proportion of CRCs were diagnosed in women in group I (34.5% < 2004 vs 54.9%>2005, P = 0.09), and a higher percentage of rectal cancer was found in age group III (34.3% < 2004 vs 40.7% > 2005, P < 0.01). Mean overall survival was 6.3 years and improved over time.ConclusionsEOCRC is not only characterised by age of onset but also by the more frequent presence of signet-ring cells, more poorly differentiated tumours, and higher risk of lymph node metastases. In the most recent years, a higher proportion of rectal cancer was found from the age of 30 years, and a higher proportion of CRCs were diagnosed in females below the age of 30 years.
| S-EPMC9292775 | biostudies-literature
Project description:IntroductionHigh-cost patients are characterized by repeated hospitalizations, and inpatient cost accounts for a large proportion of their total health care spending. This study aimed to assess the occurrence and costs of potentially preventable hospitalizations and explore contributing factors among high-cost patients in rural China.MethodsWe examined a population-based sample of patients using the 2016 New Rural Cooperative Medical Scheme in Dangyang city, China. Eighteen thousand forty-three high-cost patients were identified. A validated tool and logistic regression analysis were used to determine preventable hospitalizations and their patient-level and supply-side factors.ResultsHigh-cost patients were older (average age of 54 years) than non-high-cost patients (50 years) and more likely to come from poverty-stricken families. The occurrence of preventable hospitalization was 21.65% among high-cost patients. The proportion of preventable inpatient cost in total inpatient and outpatient expenditure among high-cost patients (5.81%) was lower than that of non-high-cost patients (7.88%) but accounted for 75.87% of the overall preventable inpatient cost. High-cost patients with more hospitalizations were more likely to experience preventable hospitalization, and those with heart failure, COPD, diabetes and mixed conditions were at a higher risk of preventable hospitalization, while those with more outpatient visits were less likely to show preventable hospitalization.ConclusionsThe occurrence of preventable hospitalization among high-cost patients in rural China was sizeable. The preventable inpatient cost of the overall population was concentrated among high-cost patients. Interventions such as improving preventive care and disease management targeting high-cost patients within counties may improve patients' health outcomes and quality of life and reduce overall preventable inpatient cost.
| S-EPMC8861072 | biostudies-literature
Project description:Background and objectivesAlthough patients with CKD are commonly hospitalized, little is known about those with frequent hospitalization and/or longer lengths of stay (high inpatient use). The objective of this study was to explore clinical characteristics, patterns of hospital use, and potentially preventable acute care encounters among patients with CKD with at least one hospitalization.Design, setting, participants, & measurementsWe identified all adults with nondialysis CKD (eGFR<60 ml/min per 1.73 m2) in Alberta, Canada between January 1 and December 31, 2009, excluding those with prior kidney failure. Patients with CKD were linked to administrative data to capture clinical characteristics and frequency of hospital encounters, and they were followed until death or end of study (December 31, 2012). Patients with one or more hospital encounters were categorized into three groups: persistent high inpatient use (upper 5% of inpatient use in 2 or more years), episodic high use (upper 5% in 1 year only), or nonhigh use (lower 95% in all years). Within each group, we calculated the proportion of potentially preventable hospitalizations as defined by four CKD-specific ambulatory care sensitive conditions: heart failure, hyperkalemia, volume overload, and malignant hypertension.ResultsDuring a median follow-up of 3 years, 57,007 patients with CKD not on dialysis had 118,671 hospitalizations, of which 1.7% of patients were persistent high users, 12.3% were episodic high users, and 86.0% were nonhigh users of hospital services. Overall, 24,804 (20.9%) CKD-related ambulatory care sensitive condition encounters were observed in the cohort. The persistent and episodic high users combined (14% of the cohort) accounted for almost one half (45.5%) of the total ambulatory care sensitive condition hospitalizations, most of which were attributed to heart failure and hyperkalemia. Risk of hospitalization for any CKD-specific ambulatory care sensitive condition was higher among older patients, higher CKD stage, lower income, registered First Nations status, and those with poor attachment to primary care.ConclusionsMany hospitalizations among patients with CKD and high inpatient use are ambulatory care sensitive condition related, suggesting opportunities to improve outcomes and reduce cost by focusing on better community-based care for this population.
| S-EPMC5108197 | biostudies-literature
Project description:Despite a decrease in the incidence of colorectal cancer (CRC) over the last 40 years, the incidence of CRC in people under 50 years old is increasing around the globe. Early onset (50 years old) and late onset (65 years old) CRC appear to have differences in their clinicopathological and genetic features, but it is unclear if there are differences in the tumor microenvironment. We hypothesized that the immune microenvironment of early onset CRC is distinct from late onset CRC and promotes tumor progression. We used Nanostring immune profiling to analyze mRNA expression of immune genes in FFPE surgical specimens from patients with early (N=40) and late onset (N=39) CRC. We found three genes, SAA1, C7, and CFD, have increased expression in early onset colorectal cancer and distinct immune signatures based on the tumor location. After adjusting for clinicopathological features, increased expression of CFD and SAA1 were associated with worse progression free survival and increased expression of C7 was associated with worse overall survival. We also performed gain of function experiments with CFD and SAA1 in subcutaneous tumor murine models and found that CFD is associated with higher tumor volumes, impacted several immune genes and impacted three genes in mice that were also found to be differentially expressed in early onset CRC (EGR1, PSMB9, CXCL9). Our data demonstrate that the immune microenvironment, characterized by a distinct innate immune response signature in early onset CRC, is unique, location dependent, and might contribute to worse outcomes.
2021-05-25 | GSE175433 | GEO
Project description:Background: Causative genes for autosomal dominantly inherited familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC) have been well characterized. There is, however, another 10-15 % early onset colorectal cancer (CRC) whose genetic components are currently unknown. In this study, we used DNA chip technology to systematically search for genes differentially expressed in early onset CRC. Keywords: disease state analysis
2007-03-20 | GSE4107 | GEO
Project description:The global incidence of early-onset colorectal cancer (EO-CRC) is rapidly rising. However, the reason for this rise in incidence as well as the genomic characteristics of EO-CRC remain largely unknown. We performed whole-exome sequencing in 47 cases of EO-CRC and targeted deep sequencing in 833 cases of CRC. Mutational profiles of EO-CRC were compared with previously published large-scale studies. EO-CRC and The Cancer Genome Atlas (TCGA) data were further investigated according to copy number profiles and mutation timing. We classified colorectal cancer into three subgroups: the hypermutated group consisted of mutations in POLE and mismatch repair genes; the whole-genome doubling group had early functional loss of TP53 that led to whole-genome doubling and focal oncogene amplification; the genome-stable group had mutations in APC and KRAS, similar to conventional colon cancer. Among non-hypermutated samples, whole-genome doubling was more prevalent in early-onset than in late-onset disease (54% vs 38%, Fisher's exact P = 0.04). More than half of non-hypermutated EO-CRC cases involved early TP53 mutation and whole-genome doubling, which led to notable differences in mutation frequencies between age groups. Alternative carcinogenesis involving genomic instability via loss of TP53 may be related to the rise in EO-CRC.
| S-EPMC8080557 | biostudies-literature
Project description:BackgroundRates of early-onset colorectal cancer (eoCRC), defined as disease diagnosed at <50 years of age, are increasing. The incidence and spectrum of somatic and pathogenic germline variants (PGV) in this population are not well understood.MethodsThis cross-sectional study leveraged Tempus' clinicogenomic database, including de-identified records of patients diagnosed with CRC between 2000-2022, to analyze and compare eoCRC and average-onset colorectal cancer (aoCRC, disease diagnosed ≥50 years of age) patients. The frequency and spectrum of somatic mutations and PGVs in patients with eoCRC and aoCRC were evaluated and compared.ResultsAmong 11,006 participants in this study, 57% were male, 76% were white, and 80% had stage 4 disease. Within the total cohort, 2379 had eoCRC and 8627 had aoCRC. Among patients with eoCRC, 4.2% had a tumor with high microsatellite instability and/or deficient mismatch repair (MSI-H/dMMR) and 6.8% with aoCRC had an MSI-H/dMMR tumor (p < 0.001). The most frequent somatic mutations involved TP53, APC, and KRAS, with the most significant difference in BRAF, which was more frequently mutated in aoCRC (9.8% vs. 4.7%, p < 0.0001). In total, 1413 (59.4%) eoCRC and 4898 (56.8%) aoCRC patients had matched normal specimen (blood or saliva) sequencing and a PGV was identified in 6.9% of eoCRC and 5.0% of aoCRC patients.ConclusionsSomatic and germline mutation profiles were similar for eoCRC and aoCRC patients and may not adequately explain differences in tumor behavior and age of disease onset.
| S-EPMC11899610 | biostudies-literature