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- Title
Methylation status of COX-2 in blood leukocyte DNA and risk of gastric cancer in a high-risk Chinese population.
- Authors
Hui-juan Su; Yang Zhang; Lian Zhang; Jun-ling Ma; Ji-You Li; Kai-feng Pan; Wei-cheng You; Su, Hui-juan; Zhang, Yang; Zhang, Lian; Ma, Jun-ling; Li, Ji-You; Pan, Kai-feng; You, Wei-cheng
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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).<bold>Conclusions: </bold>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.
- Subjects
DNA methylation; CYCLOOXYGENASE 2; LEUCOCYTES; STOMACH cancer risk factors; HEALTH of Chinese people; ASIANS; DNA; HELICOBACTER diseases; OXIDOREDUCTASES; POLYMERASE chain reaction; STOMACH tumors; CASE-control method; ODDS ratio; DISEASE complications
- Publication
BMC Cancer, 2015, Vol 15, p1
- ISSN
1471-2407
- Publication type
journal article
- DOI
10.1186/s12885-015-1962-x