Aberrant DNA methylation in ulcerative colitis without neoplasia.
OBJECTIVE
DNA methylation has been reported to correlate with the development of colitis associated cancer. We detected the promoter methylation of estrogen receptor gene (ER), TP53, p14, p16, p21 and hMLH1 in ulcerative colitis without neoplasia.


METHODS
A total of 49 specimens from 36 patients, including 36 at rectal inflammatory mucosa and 13 at terminal ileum were obtained by colonoscopic biopsies. Methylation specific polymerase chain reaction were performed to detect the methylation in promoters of the above six genes.


RESULTS
Methylation rate of ER promoter was significantly higher in the rectal mucosa than that in the ileum (76.3% vs. 46.2%, P=0.044). Moreover, ER methylation in rectal mucosa was significantly higher in relapse-remitting type compared to one attack only type cases (P=0.008), and also increased in cases longer than 7 years (P=0.036). Methylation rates of p14 or p16 were higher in rectal mucosa than those in the ileum, but the differences were not of statistic significance. Meanwhile, methylation in TP53 promoter was found in only one case, while p21 and hMLH1 methylation were negative in all cases.


CONCLUSIONS
Methylation in promoters of ER, p14 and p16 occurs in rectal inflammatory mucosa without neoplasia. Examination of ER methylation in rectal mucosa may be useful for predicting cases at high risk of neoplasia.
Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan. wangf65@yahoo.com
Fang-Yu
FY
Wang
Tomiyasu
T
Arisawa
Tomomitsu
T
Tahara
Kazuya
K
Takahama
Makoto
M
Watanabe
Ichiro
I
Hirata
Hiroshi
H
Nakano
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D003093:Colitis, Ulcerative / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; C493956:CDKN1A protein, human; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011960:Receptors, Estrogen; D025803:Tumor Suppressor Protein p14ARF; D000070957:MutL Protein Homolog 1