|Methylation status of COX-2 in blood leukocyte DNA and risk of gastric cancer in a high-risk Chinese population|
|Su, Hui-juan1; Zhang, Yang1; Zhang, Lian1; Ma, Jun-ling1; Li, Ji-You2; Pan, Kai-feng1; You, Wei-cheng1|
|关键词||DNA methylation Blood leukocyte COX-2 Gastric cancer|
|WOS标题词||Science & Technology|
|关键词[WOS]||HELICOBACTER-PYLORI ; PROMOTER METHYLATION ; CYCLOOXYGENASE-2 EXPRESSION ; GENE-EXPRESSION ; CPG ISLAND ; ABERRANT METHYLATION ; EPITHELIAL-CELLS ; PROSTATE-CANCER ; BREAST-CANCER ; OVEREXPRESSION|
Background: Methylation is a common epigenetic modification which may play a crucial role in cancer development. To investigate the association between methylation of COX-2 in blood leukocyte DNA and risk of gastric cancer (GC), a nested case-control study was conducted in Linqu County, Shandong Province, a high risk area of GC in China.
Methods: Association between blood leukocyte DNA methylation of COX-2 and risk of GC was investigated in 133 GCs and 285 superficial gastritis (SG)/ chronic atrophic gastritis (CAG). The temporal trend of COX-2 methylation level during GC development was further explored in 74 pre-GC and 95 post-GC samples (including 31 cases with both pre- and post-GC samples). In addition, the association of DNA methylation and risk of progression to GC was evaluated in 74 pre-GC samples and their relevant intestinal metaplasia (IM)/dysplasia (DYS) controls. Methylation level was determined by quantitative methylation-specific PCR (QMSP). Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated by unconditional logistic regression analysis.
Results: The medians of COX-2 methylation levels were 2.3 % and 2.2 % in GC cases and controls, respectively. No significant association was found between COX-2 methylation and risk of GC (OR, 1.15; 95 % CI: 0.70-1.88). However, the temporal trend analysis showed that COX-2 methylation levels were elevated at 1-4 years ahead of clinical GC diagnosis compared with the year of GC diagnosis (3.0 % vs. 2.2 %, p = 0.01). Further validation in 31 GCs with both pre- and post-GC samples indicated that COX-2 methylation levels were significantly decreased at the year of GC diagnosis compared with pre-GC samples (1.5 % vs. 2.5 %, p = 0.02). No significant association between COX-2 methylation and risk of progression to GC was found in subjects with IM (OR, 0.50; 95 % CI: 0.18-1.42) or DYS (OR, 0.70; 95 % CI: 0.23-2.18). Additionally, we found that elder people had increased risk of COX-2 hypermethylation (OR, 1.55; 95 % CI: 1.02-2.36) and subjects who ever infected with H. pylori had decreased risk of COX-2 hypermethylation (OR, 0.54; 95 % CI: 0.34-0.88).
Conclusions: COX-2 methylation exists in blood leukocyte DNA but at a low level. COX-2 methylation levels in blood leukocyte DNA may change during GC development.
|项目编号||30921140311 ; 81171989 ; 30801346 ; 2010CB529303|
|资助机构||Natural Science Foundation of China ; National Natural Science Foundation of China ; National Basic Research Program of China|
|作者单位||1.Peking Univ, Canc Hosp & Inst, Dept Canc Epidemiol, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing 100871, Peoples R China|
2.Peking Univ, Canc Hosp & Inst, Dept Pathol, Beijing 100871, Peoples R China
|Su, Hui-juan,Zhang, Yang,Zhang, Lian,et al. Methylation status of COX-2 in blood leukocyte DNA and risk of gastric cancer in a high-risk Chinese population[J]. BMC CANCER,2015,15.|
|APA||Su, Hui-juan.,Zhang, Yang.,Zhang, Lian.,Ma, Jun-ling.,Li, Ji-You.,...&You, Wei-cheng.(2015).Methylation status of COX-2 in blood leukocyte DNA and risk of gastric cancer in a high-risk Chinese population.BMC CANCER,15.|
|MLA||Su, Hui-juan,et al."Methylation status of COX-2 in blood leukocyte DNA and risk of gastric cancer in a high-risk Chinese population".BMC CANCER 15(2015).|