Dataset Information

Association between risk factors, molecular features and CpG island methylator phenotype colorectal cancer among different age groups in a Taiwanese cohort.

ABSTRACT:

Background

CpG island methylator phenotype (CIMP) represents a carcinogenesis pathway of colorectal cancer (CRC) and the association between CIMP CRC, molecular features and risk factors in East Asian population is less studied.

Methods

We prospectively enrolled newly diagnosed CRC patients at the National Taiwan University Hospital. Clinicopathological data and risk factors for CRC were collected during interview. The tumour samples were subjected to CIMP, RAS/BRAF mutation and microsatellite instability tests. CIMP-high was determined when ≧3 methylated loci of p16, MINT1, MINT2, MINT31 and MLH1 were identified. Multivariate logistic regression was used to evaluate the association between risk factors and CIMP-high CRC.

Results

Compared with CIMP-low/negative CRC, CIMP-high CRC was associated with more stage IV disease, BRAF V600E mutation and high body mass index (BMI ≧ 27.5 kg/m²) in younger patients (age < 50 y), and more right-sided tumour, BRAF V600E mutation, MSI-high and colorectal polyp in elder patients (age ≧ 50 y). Multivariate analyses showed that BMI ≧27.5 kg/m² was significantly associated with CIMP-high CRC in younger patients.

Conclusions

We identified distinct clinicopathological features for CIMP-high CRC among different age groups in Taiwan. Our data suggest the association between BMI ≧27.5 kg/m² and CIMP-high CRC in patients younger than 50 years.

SUBMITTER: Chen KH

PROVIDER: S-EPMC8257672 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Publications

Association between risk factors, molecular features and CpG island methylator phenotype colorectal cancer among different age groups in a Taiwanese cohort.

Chen Kuo-Hsing KH Lin Liang-In LI Yuan Chang-Tsu CT Tseng Li-Hui LH Chao Yu-Liang YL Liang Yi-Hsin YH Liang Jin-Tung JT Lin Been-Ren BR Cheng Ann-Lii AL Yeh Kun-Huei KH

British journal of cancer 20210412 1

<h4>Background</h4>CpG island methylator phenotype (CIMP) represents a carcinogenesis pathway of colorectal cancer (CRC) and the association between CIMP CRC, molecular features and risk factors in East Asian population is less studied.<h4>Methods</h4>We prospectively enrolled newly diagnosed CRC patients at the National Taiwan University Hospital. Clinicopathological data and risk factors for CRC were collected during interview. The tumour samples were subjected to CIMP, RAS/BRAF mutation and m ...[more]

PMID: 33846524

Similar Datasets

Project description:Background & aimsSubgroups of colorectal carcinomas (CRCs) characterized by DNA methylation anomalies are termed CpG island methylator phenotype (CIMP)1, CIMP2, or CIMP-negative. The pathogenesis of CIMP1 colorectal carcinomas, and their effects on patients' prognoses and responses to treatment, differ from those of other CRCs. We sought to identify genetic somatic alterations associated with CIMP1 CRCs.MethodsWe examined genomic DNA samples from 100 primary CRCs, 10 adenomas, and adjacent normal-appearing mucosae from patients undergoing surgery or colonoscopy at 3 tertiary medical centers. We performed exome sequencing of 16 colorectal tumors and their adjacent normal tissues. Extensive comparison with known somatic alterations in CRCs allowed segregation of CIMP1-exclusive alterations. The prevalence of mutations in selected genes was determined from an independent cohort.ResultsWe found that genes that regulate chromatin were mutated in CIMP1 CRCs; the highest rates of mutation were observed in CHD7 and CHD8, which encode members of the chromodomain helicase/adenosine triphosphate-dependent chromatin remodeling family. Somatic mutations in these 2 genes were detected in 5 of 9 CIMP1 CRCs. A prevalence screen showed that nonsilencing mutations in CHD7 and CHD8 occurred significantly more frequently in CIMP1 tumors (18 of 42 [43%]) than in CIMP2 (3 of 34 [9%]; P < .01) or CIMP-negative tumors (2 of 34 [6%]; P < .001). CIMP1 markers had increased binding by CHD7, compared with all genes. Genes altered in patients with CHARGE syndrome (congenital malformations involving the central nervous system, eye, ear, nose, and mediastinal organs) who had CHD7 mutations were also altered in CRCs with mutations in CHD7.ConclusionsAberrations in chromatin remodeling could contribute to the development of CIMP1 CRCs. A better understanding of the biological determinants of CRCs can be achieved when these tumors are categorized according to their epigenetic status.

Dataset Information

Association between risk factors, molecular features and CpG island methylator phenotype colorectal cancer among different age groups in a Taiwanese cohort.

Background

Methods

Results

Conclusions

Publications

Association between risk factors, molecular features and CpG island methylator phenotype colorectal cancer among different age groups in a Taiwanese cohort.

Similar Datasets

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