RUNX3 methylation and expression associated with advanced precancerous gastric lesions in a Chinese population.
Runt-related transcription factor 3 (RUNX3) is a tumor suppressor of gastric cancer. Our study aimed to investigate the correlation of RUNX3 methylation, expression and the risk of advanced gastric lesions, based on a high-risk population in Linqu County, Shandong Province, China. Methylation status of RUNX3 was determined by methylation-specific polymerase chain reaction, and expression was detected by immunohistochemical analysis in 1113 subjects with different gastric lesions. Results showed that the frequency of RUNX3 methylation was significantly increased in subjects with advanced gastric lesions. The odds ratios (ORs) were 2.09 [95% confidence interval (CI): 1.49-2.94] for intestinal metaplasia (IM), 3.22 (95% CI: 2.33-4.47) for indefinite dysplasia (Ind DYS) and 2.03 (95% CI: 1.23-3.37) for dysplasia (DYS) compared with superficial gastritis/chronic atrophic gastritis. Stratified analysis indicated that the frequency of RUNX3 methylation was higher in subjects with Helicobacter pylori infection (OR, 2.74; 95% CI: 2.00-3.76). Moreover, there was a reverse grade-response relationship between the level of RUNX3 expression and risk of gastric lesions. Among subjects with mild, moderate or heavy expression, the risk was decreased by 41, 59 or 80% for IM (P(trend) < 0.0001); 40, 64 or 74% for Ind DYS (P(trend) < 0.0001) and 28, 59 or 51% for DYS (P(trend) = 0.045), respectively. Furthermore, RUNX3 expression was negatively associated with increased frequency of RUNX3 methylation (OR, 0.76; 95% CI: 0.59-0.98). These findings suggest that RUNX3 may play important roles in the development of advanced gastric lesions.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Haidian District, Beijing 100142, China.
Wen-Qing
WQ
Li
Kai-Feng
KF
Pan
Yang
Y
Zhang
Cai-Xuan
CX
Dong
Lian
L
Zhang
Jun-Ling
JL
Ma
Tong
T
Zhou
Ji-You
JY
Li
Wei-Cheng
WC
You
D000328:Adult; D044466:Asian People / Q000235:genetics*; D015331:Cohort Studies; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D005757:Gastritis, Atrophic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016481:Helicobacter Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology; D016480:Helicobacter pylori / Q000235:genetics; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D050677:Core Binding Factor Alpha 3 Subunit; D004273:DNA, Neoplasm; C493729:Runx3 protein, human