Clinical Characteristics and Outcomes of Colorectal Cancer in the ColoCare Study: Differences by Age of Onset.
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SUBMITTER: Himbert C
PROVIDER: S-EPMC8345133 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundColorectal cancer is a leading cause of cancer death. Biomarkers to predict treatment outcomes are needed, as is evidence whether postdiagnosis diet and lifestyle can affect well-being and clinical outcomes. The international ColoCare Consortium aims to identify new biologic markers (e.g., metabolomic, transcriptomic, metagenomic, genetic, epigenetic, proteomic markers) that predict clinical outcomes, and to characterize associations between modifiable risk factors (e.g., diet, supplement use, physical activity) with short-term and long-term patient-reported and clinical outcomes among patients with colorectal cancer.Methods/Results: ColoCare is recruiting newly diagnosed patients with colorectal cancer across six sites in the United States and one site in Germany. As of April 2018, we have recruited >2,000 patients across all sites. Our projected enrollment is >4,000 multiethnic patients with colorectal cancer. The study includes uniformly collected, comprehensive sets of data and biospecimens at multiple time points up to 5 years after diagnosis. Treatment and clinical data are abstracted from medical records and centrally harmonized. Biospecimens are archived according to standardized procedures. Our initial studies demonstrated metabolic differences in adipose tissue types. We further reported on associations of biological factors (e.g., inflammation, DNA methylation, metabolomics) with lifestyle factors (e.g., adiposity, smoking, physical activity, dietary supplement use) or joint associations with clinical outcomes.ConclusionsColoCare is a consortium for the investigation of multilevel factors relevant to colorectal cancer survivorship.ImpactThe combination of a comprehensive set of biospecimens collected at multiple time points, jointly with detailed assessments of health behaviors and other prognostic factors, results in a unique resource that facilitates wide-ranging, innovative, and impactful research on colorectal cancer.
| S-EPMC6420345 | biostudies-literature
Project description:BackgroundMetabolic and transcriptomic differences between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) compartments, particularly in the context of obesity, may play a role in colorectal carcinogenesis. We investigated the differential functions of their metabolic compositions.ObjectivesBiochemical differences between adipose tissues (VAT compared with SAT) in patients with colorectal carcinoma (CRC) were investigated by using mass spectrometry metabolomics and gene expression profiling. Metabolite compositions were compared between VAT, SAT, and serum metabolites. The relation between patients' tumor stage and metabolic profiles was assessed.DesignPresurgery blood and paired VAT and SAT samples during tumor surgery were obtained from 59 CRC patients (tumor stages I-IV) of the ColoCare cohort. Gas chromatography time-of-flight mass spectrometry and liquid chromatography quadrupole time-of-flight mass spectrometry were used to measure 1065 metabolites in adipose tissue (333 identified compounds) and 1810 metabolites in serum (467 identified compounds). Adipose tissue gene expression was measured by using Illumina's HumanHT-12 Expression BeadChips.ResultsCompared with SAT, VAT displayed elevated markers of inflammatory lipid metabolism, free arachidonic acid, phospholipases (PLA2G10), and prostaglandin synthesis-related enzymes (PTGD/PTGS2S). Plasmalogen concentrations were lower in VAT than in SAT, which was supported by lower gene expression of FAR1, the rate-limiting enzyme for ether-lipid synthesis in VAT. Serum sphingomyelin concentrations were inversely correlated (P = 0.0001) with SAT adipose triglycerides. Logistic regression identified lipids in patients' adipose tissues, which were associated with CRC tumor stage.ConclusionsAs one of the first studies, we comprehensively assessed differences in metabolic, lipidomic, and transcriptomic profiles between paired human VAT and SAT and their association with CRC tumor stage. We identified markers of inflammation in VAT, which supports prior evidence regarding the role of visceral adiposity and cancer.
| S-EPMC4515859 | biostudies-literature
Project description:ObjectiveNeuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease preferentially affects the optic nerve and the spinal cord. The first attack usually occurs in the third or fourth decade, though patients with disease onset in the fifties or later are not uncommon. This study aimed to investigate the clinical characteristics and prognosis in patients with different age of onset and to explore the correlations between age of onset and clinical characteristics and prognostic outcomes.MethodWe retrospectively reviewed the medical records of 298 NMOSD patients diagnosed according to the 2015 updated version of diagnostic criteria. Patients were divided into early-onset NMOSD (EO-NMOSD) (<50 years at disease onset) and late-onset NMOSD (LO-NMOSD) (≥50 years at disease onset) based on the age of disease onset. LO-NMOSD patients were divided into two subgroups: relative-late-onset NMOSD (RLO-NMOSD) (50~70 years at disease onset) and very-late-onset NMOSD (≥70 years at disease onset). Clinical characteristics, laboratory findings, neuroimaging features, and prognostic outcomes were investigated.ResultsCompared to EO-NMOSD patients, patients with LO-NMOSD showed more frequent transverse myelitis (TM) (58.20% vs. 36.00%, p = 0.007) while less frequent optic neuritis (ON) (23.10% vs. 34.80%, p = 0.031) and brainstem/cerebral attacks (7.50% vs. 18.30%, p = 0.006) as the first attack. Patients with LO-NMOSD showed less frequent relapses, higher Expanded Disability Status Scale (EDSS) score at the last follow-up, fewer NMOSD-typical brain lesions, and longer segments of spinal cord lesions. Patients with older onset age showed a higher proportion of increased protein levels in cerebrospinal fluid during the acute phase of attacks. Age at disease onset positively correlated with length of spinal cord lesions at first attack and at last follow-up, negatively correlated with ARR-1 (ARR excluding the first attack, calculated from disease onset to final follow-up), irrespective of AQP4-IgG serostatus. Patients with older age at disease onset progressed to severe motor disability sooner, and age of onset positively correlated with EDSS score at the last follow-up, irrespective of AQP4-IgG serostatus.ConclusionAge of disease onset affects clinical characteristics and prognosis outcomes of patients with NMOSD.
| S-EPMC9772011 | 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:BackgroundFusobacterium nucleatum (Fn), a bacterium associated with a wide spectrum of infections, has emerged as a key microbe in colorectal carcinogenesis. However, the underlying mechanisms and clinical relevance of Fn in colorectal cancer (CRC) remain incompletely understood.Patients and methodsWe examined associations between Fn abundance and clinicopathologic characteristics among 105 treatment-naïve CRC patients enrolled in the international, prospective ColoCare Study. Electronic medical charts, including pathological reports, were reviewed to document clinicopathologic features. Quantitative real-time polymerase chain reaction (PCR) was used to amplify/detect Fn DNA in preoperative fecal samples. Multinomial logistic regression was used to analyze associations between Fn abundance and patient sex, age, tumor stage, grade, site, microsatellite instability, body mass index (BMI), alcohol consumption, and smoking history. Cox proportional hazards models were used to investigate associations of Fn abundance with overall survival in adjusted models.ResultsCompared to patients with undetectable or low Fn abundance, patients with high Fn abundance (n = 22) were 3-fold more likely to be diagnosed with rectal versus colon cancer (odds ratio [OR] = 3.01; 95% confidence interval [CI], 1.06-8.57; P = .04) after adjustment for patient sex, age, BMI, and study site. Patients with high Fn abundance also had a 5-fold increased risk of being diagnosed with rectal cancer versus right-sided colon cancer (OR = 5.32; 95% CI, 1.23-22.98; P = .03). There was no statistically significant association between Fn abundance and overall survival.ConclusionOur findings suggest that Fn abundance in fecal samples collected prior to surgery varies by tumor site among treatment-naïve CRC patients. Overall, fecal Fn abundance may have diagnostic and prognostic significance in the clinical management of CRC.
| S-EPMC8390557 | biostudies-literature
Project description:Our aim was to characterize and validate that the location and age of onset of the tumor are both important criteria to classify colorectal cancer (CRC). We analyzed clinical and molecular characteristics of early-onset CRC (EOCRC) and late-onset CRC (LOCRC), and we compared each tumor location between both ages-of-onset. In right-sided colon tumors, early-onset cases showed extensive Lynch syndrome (LS) features, with a relatively low frequency of chromosomal instability (CIN), but a high CpG island methylation phenotype. Nevertheless, late-onset cases showed predominantly sporadic features and microsatellite instability cases due to BRAF mutations. In left colon cancers, the most reliable clinical features were the tendency to develop polyps as well as multiple primary CRC associated with the late-onset subset. Apart from the higher degree of CIN in left-sided early-onset cancers, differential copy number alterations were also observed. Differences among rectal cancers showed that early-onset rectal cancers were diagnosed at later stages, had less association with polyps, and more than half of them were associated with a familial LS component. Stratifying CRC according to both location and age-of-onset criteria is meaningful, not only because it correlates the resulting categories with certain molecular bases, but with the confirmation across larger studies, new therapeutical algorithms could be defined according to this subclassification.
| S-EPMC6413061 | biostudies-literature
Project description:Background/aimsThis nationwide study was undertaken to determine differences in clinicopathologic characteristics and survival of patients with colorectal cancer (CRC) according to age using big data from the Korean National Health Insurance Service (NHIS).MethodsThe NHIS data including quality assessment of CRC by the Health Insurance Review & Assessment Service in Korea between 2011 and 2014 were analyzed. Based on age, patients were divided into three groups: not-old patients (< 65), young-old patients (65 to 74 years old) and old-old patients (≥ 75 years old).ResultsWe included 71,513 CRC patients. The median follow-up duration was 3.2 years (range, 0.003 to 5.5). Male patients constituted 60%. The median age of patients was 65 years (range, 18 to 102). Colon was the cancer site in 59.8% of not-old patients, 62.9% of young-old patients, and 66.1% of old-old patients. Compared to not-old patients, young-old and old-old patients were more likely to be diagnosed with colon adenocarcinoma and well/moderate differentiation or adequate differentiation (all p < 0.001). Old patients underwent more emergency operation (p < 0.001) and received less adjuvant therapy in stage I-III (p < 0.001). The probability of 3-year survival of young-old or old-old patients was worse than that for not-old patients (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.46 to 1.64) (HR, 3.19; 95% CI, 3.03 to 3.37).ConclusionOld patients with CRC show different histology from younger patients. They are more frequently to have colon as primary lesion. They undergo less adjuvant therapy. Further studies and evidence-based guidelines for older patients with CRC are warranted to improve their outcome.
| S-EPMC8273826 | biostudies-literature
Project description:AimsChildhood-onset hypertrophic cardiomyopathy (HCM) is far less common than adult-onset disease, thus natural history is not well characterized. We aim to describe the characteristics and outcomes of childhood-onset HCM.Methods and resultsWe performed an observational cohort study of 7677 HCM patients from the Sarcomeric Human Cardiomyopathy Registry (SHaRe). Hypertrophic cardiomyopathy patients were stratified by age at diagnosis [<1 year (infancy), 1-18 years (childhood), >18 years (adulthood)] and assessed for composite endpoints reflecting heart failure (HF), life-threatening ventricular arrhythmias, atrial fibrillation (AF), and an overall composite that also included stroke and death. Stratifying by age of diagnosis, 184 (2.4%) patients were diagnosed in infancy; 1128 (14.7%) in childhood; and 6365 (82.9%) in adulthood. Childhood-onset HCM patients had an ∼2%/year event rate for the overall composite endpoint, with ventricular arrhythmias representing the most common event in the 1st decade following baseline visit, but HF and AF becoming more common by the end of the 2nd decade. Sarcomeric variants were more common in childhood-onset HCM (63%) and carried a worse prognosis than non-sarcomeric disease, including a greater than two-fold increased risk of HF [HRadj 2.39 (1.36-4.20), P = 0.003] and 67% increased risk of the overall composite outcome [HRadj 1.67 (1.16-2.41), P = 0.006]. When compared with adult-onset HCM, childhood-onset was 36% more likely to develop life-threatening ventricular arrhythmias [HRadj 1.36 (1.03-1.80)] and twice as likely to require transplant or ventricular assist device [HRadj 1.99 (1.23-3.23)].ConclusionPatients with childhood-onset HCM are more likely to have sarcomeric disease, carry a higher risk of life-threatening ventricular arrythmias, and have greater need for advanced HF therapies. These findings provide insight into the natural history of disease and can help inform clinical risk stratification.
| S-EPMC8139852 | biostudies-literature
Project description:Metabolomics is a valuable tool for biomarker screening of colorectal cancer (CRC). In this study, we profiled the urinary metabolomes of patients enrolled in a prospective patient cohort (ColoCare). We aimed to describe changes in the metabolome in the longer clinical follow-up and describe initial predictors as candidate markers with possibly prognostic significance.In total, 199 urine samples from CRC patients pre-surgery (n=97), 1-8 days post-surgery (n=12) and then after 6 and 12 months (n=52 and 38, respectively) were analyzed using both GC-MS and 1H-NMR. Both datasets were analyzed separately with built in uni- and multivariate analyses of Metaboanalyst 2.0. Furthermore, adjusted linear mixed effects regression models were constructed.Many concentrations of the metabolites derived from the gut microbiome were affected by CRC surgery, presumably indicating a tumor-induced shift in bacterial species. Associations of the microbial metabolites with disease stage indicate an important role of the gut microbiome in CRC.We were able to differentiate the metabolite profiles of CRC patients prior to surgery from those at any post-surgery timepoint using a multivariate model containing 20 marker metabolites (AUCROC=0.89; 95% CI:0.84-0.95).To the best of our knowledge, this is one of the first metabolomic studies to follow CRC patients in a prospective setting with repeated urine sampling over time. We were able to confirm markers initially identified in case-control studies and pin point metabolites which may serve as candidates for prognostic biomarkers of CRC.
| S-EPMC5730072 | biostudies-literature
Project description:Smoking tobacco is a known risk factor for the development of colorectal cancer and for mortality associated with the disease. Smoking has been reported to be associated with changes in DNA methylation in blood and in lung tumour tissues, although there has been scant investigation of how epigenetic factors may be implicated in the increased risk of developing colorectal cancer. To identify epigenetic changes associated with smoking behaviours, we performed epigenome-wide analysis of DNA methylation in colorectal tumours from 36 never-smokers, 47 former smokers, and 13 active smokers, and in adjacent mucosa from 49 never-smokers, 64 former smokers, and 18 active smokers. Our analyses identified 15 CpG sites within the APC 1A promoter that were significantly hypermethylated and 14 CpG loci within the NFATC1 gene body that were significantly hypomethylated (pLIS < 1 × 10-5 ) in the tumours of active smokers. The APC 1A promoter was hypermethylated in 7 of 36 tumours from never-smokers (19%), 12 of 47 tumours from former smokers (26%), and 8 of 13 tumours from active smokers (62%). Promoter hypermethylation was positively associated with duration of smoking (Spearman rank correlation, ρ = 0.26, p = 0.03) and was confined to tumours, with hypermethylation never being observed in adjacent mucosa. Further analysis of adjacent mucosa revealed significant hypomethylation of four loci associated with the TNXB gene in tissue from active smokers. Our findings provide exploratory evidence for hypermethylation of the key tumour suppressor gene APC being implicated in smoking-associated colorectal carcinogenesis. Further work is required to establish the validity of our observations in independent cohorts. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
| S-EPMC5647242 | biostudies-literature