| Title | Methylation status of COX-2 in blood leukocyte DNA and risk of gastric cancer in a high-risk Chinese population |
| Authors | Su, Hui-juan Zhang, Yang Zhang, Lian Ma, Jun-ling Li, Ji-You Pan, Kai-feng You, Wei-cheng |
| Affiliation | Peking Univ, Canc Hosp & Inst, Dept Canc Epidemiol, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing 100871, Peoples R China. Peking Univ, Canc Hosp & Inst, Dept Pathol, Beijing 100871, Peoples R China. |
| Keywords | DNA methylation Blood leukocyte COX-2 Gastric cancer HELICOBACTER-PYLORI PROMOTER METHYLATION CYCLOOXYGENASE-2 EXPRESSION GENE-EXPRESSION CPG ISLAND ABERRANT METHYLATION EPITHELIAL-CELLS PROSTATE-CANCER BREAST-CANCER OVEREXPRESSION |
| Issue Date | 2015 |
| Publisher | BMC CANCER |
| Citation | BMC CANCER.2015,15. |
| Abstract | 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. |
| URI | http://hdl.handle.net/20.500.11897/435848 |
| ISSN | 1471-2407 |
| DOI | 10.1186/s12885-015-1962-x |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 北京肿瘤医院 |
