Methylation of the oestrogen receptor gene in non-neoplastic epithelium as a marker of colorectal neoplasia risk in longstanding and extensive ulcerative colitis.
BACKGROUND
Surveillance colonoscopy is widely recommended in patients with longstanding and extensive ulcerative colitis (UC) in order to detect colorectal neoplasia at an early stage. However, it still remains questionable whether surveillance colonoscopy effectively enables early detection of UC associated neoplasia. There is a great need for sensitive markers to identify individuals at increased risk of neoplasia. The oestrogen receptor (OR) gene shows age related methylation in the colorectal epithelium and is methylated frequently in sporadic colorectal neoplasia, suggesting that OR methylation may predispose to colorectal neoplasia.


OBJECTIVE
To clarify whether analysis of methylation of the OR gene in non-neoplastic epithelium can contribute to prediction of increased neoplasia risk in UC patients.


METHODS
A total of 165 non-neoplastic colorectal epithelia from 30 patients with longstanding and extensive UC, including 13 UC patients with neoplasia and 17 patients without, were evaluated. Methylation specific polymerase chain reaction was performed to determine the methylation status of the OR gene.


RESULTS
Methylation of the OR gene was detected in 54 of 70 (77.1%) non-neoplastic colorectal epithelia in UC with neoplasia but in only 23 of 95 (24.2%) without neoplasia. Methylation of the OR gene was significantly more frequent in non-neoplastic epithelium from UC with neoplasia than in chronic colitic epithelium from UC without neoplasia. Furthermore, in UC with neoplasia, the OR gene was extensively methylated in non-neoplastic epithelia throughout the colorectum compared with those in UC without neoplasia.


CONCLUSIONS
These results suggest that analysis of OR gene methylation may have potential as a useful marker for identifying individuals at increased risk of neoplasia among those with longstanding and extensive UC.
Fujii
S
S
Department of Surgical and Molecular Pathology, Dokkyo University School of Medicine, 880 Kitakobayashi, Mibu, Shimotsuga, Tochigi 321-0293, Japan. t-fuji@dokkyomed.ac.jp
Tominaga
K
K
Kitajima
K
K
Takeda
J
J
Kusaka
T
T
Fujita
M
M
Ichikawa
K
K
Tomita
S
S
Ohkura
Y
Y
Ono
Y
Y
Imura
J
J
Chiba
T
T
Fujimori
T
T
D000368:Aged; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003093:Colitis, Ulcerative / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D019175:DNA Methylation; D018450:Disease Progression; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D012306:Risk; D013997:Time Factors
D005819:Genetic Markers; D011960:Receptors, Estrogen