PMID- 20572039
OWN - NLM
STAT- MEDLINE
DCOM- 20101105
LR  - 20211020
IS  - 0008-543X (Print)
IS  - 1097-0142 (Electronic)
IS  - 0008-543X (Linking)
VI  - 116
IP  - 19
DP  - 2010 Oct 1
TI  - Relation between normal rectal methylation, smoking status, and the presence or 
      absence of colorectal adenomas.
PG  - 4495-501
LID - 10.1002/cncr.25348 [doi]
AB  - BACKGROUND: Colorectal cancer (CRC) is 1 of the leading causes of death in the 
      Western world. CRC develops from premalignant lesions, chiefly colorectal 
      adenomas. Currently, the most accurate and recommended screening method for 
      finding colorectal adenomas is colonoscopy performed on all individuals aged>50 
      years. However, the costs and risks associated with this procedure are relatively 
      high. The objectives of the current study were to correlate epigenetic 
      alterations that occur in normal rectal mucosa, smoking status, and age with the 
      presence or absence of concomitant colorectal adenomas and to assess the 
      potential clinical value of methylation in normal rectal biopsies as a screening 
      assay for the presence of polyps and, hence, the need for a full colonoscopy. 
      METHODS: One hundred thirteen normal rectal mucosal biopsies from 113 patients 
      were studied. DNA was extracted, modified with sodium bisulfite, and subjected to 
      real-time quantitative, methylation-specific polymerase chain reaction analysis 
      for the following genes: adenomatous polyposis coli (APC); cadherin 1, type 1, 
      E-cadherin (epithelial) (CDH1); estrogen receptor 1 (ESR1); cytokine high in 
      normal 1 (HIN1); hyperplastic polyposis protein 1 (HPP1); O-6 methylguanine-DNA 
      methyltransferase (MGMT); neural epidermal growth factor-like 1 (NELL1); splicing 
      factor 3B, 14-kDa subunit (p14); cyclin-dependent kinase (CDK) inhibitor 2B 
      (inhibits CDK4) (p15); retinoic acid receptor beta (RARbeta); somatostatin (SST); 
      tachykinin, precursor 1 (TAC1); and tissue inhibitor of metalloproteinase (TIMP) 
      metallopeptidase inhibitor 3 (TIMP3). Data were then analyzed using several 
      proprietary software programs. RESULTS: By using several sets of genes, clinical 
      characteristics, and multivariate analyses, the authors developed a prediction 
      model for the presence of concomitant colorectal adenomas at the time of rectal 
      biopsy. They also observed strong correlations between smoking status and rectal 
      methylation pattern and between smoking status and the presence or risk of 
      concomitant adenomas. CONCLUSIONS: A prediction model was developed for the 
      presence of colorectal adenomas based on gene methylation patterns in the normal 
      rectum. The results indicated that these genes may be involved in early stages of 
      adenoma formation. The observed epigenetic alterations in these markers may be 
      caused in part by the effects of smoking and/or age. Normal rectal methylation 
      may be useful as a biomarker for narrowing the population in need of screening 
      colonoscopy.
CI  - Copyright (c) 2010 American Cancer Society.
FAU - Paun, Bogdan C
AU  - Paun BC
AD  - Division of Gastroenterology, Department of Medicine, the Johns Hopkins 
      University School of Medicine, Baltimore, Maryland 21287, USA.
FAU - Kukuruga, Debra
AU  - Kukuruga D
FAU - Jin, Zhe
AU  - Jin Z
FAU - Mori, Yuriko
AU  - Mori Y
FAU - Cheng, Yulan
AU  - Cheng Y
FAU - Duncan, Mark
AU  - Duncan M
FAU - Stass, Sanford A
AU  - Stass SA
FAU - Montgomery, Elizabeth
AU  - Montgomery E
FAU - Hutcheon, David
AU  - Hutcheon D
FAU - Meltzer, Stephen J
AU  - Meltzer SJ
LA  - eng
GR  - R01 DK047717-07/DK/NIDDK NIH HHS/United States
GR  - R01 CA077057-06/CA/NCI NIH HHS/United States
GR  - R01 CA095323-09A2/CA/NCI NIH HHS/United States
GR  - R01 CA077057/CA/NCI NIH HHS/United States
GR  - R01 CA095323/CA/NCI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
SB  - IM
MH  - Adenoma/*genetics
MH  - Adolescent
MH  - Adult
MH  - Age Factors
MH  - Aged
MH  - Aged, 80 and over
MH  - Child
MH  - Child, Preschool
MH  - Colorectal Neoplasms/*genetics
MH  - DNA Methylation
MH  - Female
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Intestinal Mucosa/metabolism
MH  - Male
MH  - Middle Aged
MH  - Models, Statistical
MH  - Rectum/*metabolism
MH  - Risk
MH  - *Smoking
PMC - PMC2988654
MID - NIHMS251065
COIS- CONFLICT OF INTEREST DISCLOSURES The authors made no disclosures.
EDAT- 2010/06/24 06:00
MHDA- 2010/11/06 06:00
PMCR- 2010/11/19
CRDT- 2010/06/24 06:00
PHST- 2010/06/24 06:00 [entrez]
PHST- 2010/06/24 06:00 [pubmed]
PHST- 2010/11/06 06:00 [medline]
PHST- 2010/11/19 00:00 [pmc-release]
AID - 10.1002/cncr.25348 [doi]
PST - ppublish
SO  - Cancer. 2010 Oct 1;116(19):4495-501. doi: 10.1002/cncr.25348.