Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2010-3-18
pubmed:abstractText
There are two major molecular pathways to sporadic colorectal cancer, the chromosomal instability (CIN) and the CpG island methylator phenotype (CIMP) pathways. This study recruited 166 patients undergoing colonoscopy. Biopsy samples were collected from the cecum, transverse colon, sigmoid colon and rectum. DNA methylation was quantified at 'type A' (ESR1, GATA5, HIC1, HPP1, SFRP1) and 'type C' markers (MGMT, MLH1, CDKN2A, MINT2, MINT31, IGF2, CACNA1G, NEUROG1, SOCS1, RUNX3), and LINE-1. 'Type A' genes are frequently methylated in normal and neoplastic tissues, proportional to tissue age. 'Type C' methylation is more specific for neoplasia. The last five 'type C' markers comprise a CIMP panel. The mean 'type A' and CIMP-panel methylation Z-scores were calculated. In all, 88 patients had adenomatous lesions, 32 had proximal serrated polyps (PSPs) and 50 were normal. Most 'type A' genes showed direct correlations between methylation and age (ESR1, rho=0.66, P<0.0001), with higher methylation distally (ESR1, P<0.0001). On multivariate analysis, 'type A' methylation was inversely associated with colorectal adenomas (odds ratio=0.23, P<0.001), the precursor to CIN cancers. CIMP-panel methylation was significantly associated with advanced PSPs (odds ratio=5.1, P=0.009), the precursor to CIMP cancers. DNA methylation in normal mucosa varied with age and region and was associated with pathway-specific pathology. In the future, the colorectal field could yield important information and potentially inform clinical practice.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
18
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1653-62
pubmed:meshHeading
pubmed-meshheading:19966864-Adult, pubmed-meshheading:19966864-Age Factors, pubmed-meshheading:19966864-Aged, pubmed-meshheading:19966864-Aged, 80 and over, pubmed-meshheading:19966864-Colon, pubmed-meshheading:19966864-Colonoscopy, pubmed-meshheading:19966864-Colorectal Neoplasms, pubmed-meshheading:19966864-CpG Islands, pubmed-meshheading:19966864-DNA Methylation, pubmed-meshheading:19966864-Female, pubmed-meshheading:19966864-Genetic Predisposition to Disease, pubmed-meshheading:19966864-Humans, pubmed-meshheading:19966864-Intestinal Mucosa, pubmed-meshheading:19966864-Male, pubmed-meshheading:19966864-Middle Aged, pubmed-meshheading:19966864-Multivariate Analysis, pubmed-meshheading:19966864-Rectum, pubmed-meshheading:19966864-Sex Factors, pubmed-meshheading:19966864-Signal Transduction, pubmed-meshheading:19966864-Smoking, pubmed-meshheading:19966864-Young Adult
pubmed:year
2010
pubmed:articleTitle
DNA methylation within the normal colorectal mucosa is associated with pathway-specific predisposition to cancer.
pubmed:affiliation
Royal Brisbane and Women's Hospital Research Foundation Clinical Research Centre, Brisbane, Queensland, Australia. daniel.worthley@uqconnect.edu.au
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't