Dataset Information

A prospective cohort study shows unique epigenetic, genetic, and prognostic features of synchronous colorectal cancers.

ABSTRACT:

Background & aims

Synchronous colorectal neoplasias (2 or more primary carcinomas identified in the same patient) are caused by common genetic and environmental factors and can be used to study the field effect. Synchronous colon cancers have not been compared with control solitary cancers in a prospective study.

Methods

We analyzed data collected from 47 patients with synchronous colorectal cancers and 2021 solitary colorectal cancers (controls) in 2 prospective cohort studies. Tumors samples were analyzed for methylation in LINE-1 and 16 CpG islands (CACNA1G, CDKN2A [p16], CRABP1, IGF2, MLH1, NEUROG1, RUNX3, SOCS1, CHFR, HIC1, IGFBP3, MGMT, MINT1, MINT31, p14 [ARF], and WRN); microsatellite instability (MSI); the CpG island methylator phenotype (CIMP); 18q loss of heterozygosity; KRAS, BRAF, and PIK3CA mutations; and expression of beta-catenin, p53, p21, p27, cyclin D1, fatty acid synthase, and cyclooxygenase-2.

Results

Compared with patients with solitary colorectal cancer, synchronous colorectal cancer patients had reduced overall survival time (log-rank, P = .0048; hazard ratio [HR], 1.71; 95% confidence interval [CI]: 1.17-2.50; P = .0053; multivariate HR, 1.47; 95% CI: 1.00-2.17; P = .049). Compared with solitary tumors, synchronous tumors more frequently contained BRAF mutations (P = .0041), CIMP-high (P = .013), and MSI-high (P = .037). Methylation levels of LINE-1 (Spearman r = 0.82; P = .0072) and CpG island methylation (P < .0001) correlated between synchronous cancer pairs from the same individuals.

Conclusions

Synchronous colorectal cancers had more frequent mutations in BRAF, were more frequently CIMP- and MSI-high, and had a worse prognosis than solitary colorectal cancers. Similar epigenomic and epigenetic events were frequently observed within a synchronous cancer pair, suggesting the presence of a field defect.

SUBMITTER: Nosho K

PROVIDER: S-EPMC2859181 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A prospective cohort study shows unique epigenetic, genetic, and prognostic features of synchronous colorectal cancers.

Nosho Katsuhiko K Kure Shoko S Irahara Natsumi N Shima Kaori K Baba Yoshifumi Y Spiegelman Donna D Meyerhardt Jeffrey A JA Giovannucci Edward L EL Fuchs Charles S CS Ogino Shuji S

Gastroenterology 20090814 5

<h4>Background & aims</h4>Synchronous colorectal neoplasias (2 or more primary carcinomas identified in the same patient) are caused by common genetic and environmental factors and can be used to study the field effect. Synchronous colon cancers have not been compared with control solitary cancers in a prospective study.<h4>Methods</h4>We analyzed data collected from 47 patients with synchronous colorectal cancers and 2021 solitary colorectal cancers (controls) in 2 prospective cohort studies. T ...[more]

PMID: 19686742

Similar Datasets

Project description:BackgroundMortality rates are high among hospitalized patients with COVID-19, especially in those intubated on the ICU. Insight in pathways associated with unfavourable outcome may lead to new treatment strategies.MethodsWe performed a prospective cohort study of patients with COVID-19 admitted to general ward or ICU who underwent serial blood sampling. To provide insight in the pathways involved in disease progression, associations were estimated between outcome risk and serial measurements of 64 biomarkers in potential important pathways of COVID-19 infection (inflammation, tissue damage, complement system, coagulation and fibrinolysis) using joint models combining Cox regression and linear mixed-effects models. For patients admitted to the general ward, the primary outcome was admission to the ICU or mortality (unfavourable outcome). For patients admitted to the ICU, the primary outcome was 12-week mortality.FindingsA total of 219 patients were included: 136 (62%) on the ward and 119 patients (54%) on the ICU; 36 patients (26%) were included in both cohorts because they were transferred from general ward to ICU. On the general ward, 54 of 136 patients (40%) had an unfavourable outcome and 31 (23%) patients died. On the ICU, 54 out of 119 patients (45%) died. Unfavourable outcome on the general ward was associated with changes in concentrations of IL-6, IL-8, IL-10, soluble Receptor for Advanced Glycation End Products (sRAGE), vascular cell adhesion molecule 1 (VCAM-1) and Pentraxin-3. Death on the ICU was associated with changes in IL-6, IL-8, IL-10, sRAGE, VCAM-1, Pentraxin-3, urokinase-type plasminogen activator receptor, IL-1-receptor antagonist, CD14, procalcitonin, tumor necrosis factor alfa, tissue factor, complement component 5a, Growth arrest-specific 6, angiopoietin 2, and lactoferrin. Pathway analysis showed that unfavourable outcome on the ward was mainly driven by chemotaxis and interleukin production, whereas death on ICU was associated with a variety of pathways including chemotaxis, cell-cell adhesion, innate host response mechanisms, including the complement system, viral life cycle regulation, angiogenesis, wound healing and response to corticosteroids.InterpretationClinical deterioration in patients with severe COVID-19 involves multiple pathways, including chemotaxis and interleukin production, but also endothelial dysfunction, the complement system, and immunothrombosis. Prognostic markers showed considerable overlap between general ward and ICU patients, but we identified distinct differences between groups that should be considered in the development and timing of interventional therapies in COVID-19.FundingAmsterdam UMC, Amsterdam UMC Corona Fund, and Dr. C.J. Vaillant Fonds.

Dataset Information

A prospective cohort study shows unique epigenetic, genetic, and prognostic features of synchronous colorectal cancers.

Background & aims

Methods

Results

Conclusions

Publications

A prospective cohort study shows unique epigenetic, genetic, and prognostic features of synchronous colorectal cancers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets