Methylation status of COX-2 in blood leukocyte DNA and risk of gastric cancer in a high-risk Chinese population.
BMC Cancer
; 15: 979, 2015 Dec 16.
Article
em En
| MEDLINE
| ID: mdl-26674784
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
/
Povo Asiático
/
Ciclo-Oxigenase 2
/
Leucócitos
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Risk_factors_studies
Limite:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
BMC Cancer
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2015
Tipo de documento:
Article