[Association between promoter methylation of cyclooxygenase-2 and expression, and precancerous gastric lesions in a high-risk population].
OBJECTIVE
To evaluate the relationship between cyclooxygenase-2 (COX-2) methylation and expression, and precancerous gastric lesions.


METHODS
Methylation status of COX-2 was evaluated by quantitative denaturing high performance liquid chromatography (DHPLC) in 1201 subjects with different gastric lesions. COX-2 expression was assessed by immunohistochemistry and Helicobacter pylori (H pylori) infection status was determined by 13C-urea breath test (13 C-UBT).


RESULTS
The percent of COX-2 methylation was increased steadily with the severity of gastric lesions, showing 10.6% of which with superficial gastritis/chronic atrophic gastritis (SG/CAG), 11.8% with intestinal metaplasia (IM) and 13.8% with indefinite dysplasia/dysplasia (Ind DYS/DYS) (chi2 = 8.312, P = 0.016). Stratified analysis indicated that the percents of COX-2 methylation in subjects with H pylori negative still increased with the severity of gastric lesions,of 8.8% in SG/CAG, 10.6% in IM and 14.1% in Ind DYS/DYS (chi2 = 6.629, P= 0.036). Moreover,the methylated proportion of COX-2 was negatively associated with the expression in gastric lesions, from 13.3% with mild expression to 7.6% with strong expression (chi2 = 10.400, P = 0.015).


CONCLUSIONS
Our findings indicated that COX-2 methylation was significantly associated with precancerous gastric lesions and H pylori infection, suggesting that promoter methylation of COX-2 might play an important role in the progression of gastric lesions.
Nie
Xiao-Rui
XR
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, China.
Zhang
Yang
Y
Pan
Kai-Feng
KF
Zhang
Lian
L
Zhou
Tong
T
Li
Ji-You
JY
You
Wei-Cheng
WC
D000328:Adult; D002681:China / Q000453:epidemiology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology*; D016481:Helicobacter Infections / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D013272:Stomach Diseases / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology
D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human