Genetic variants in cyclooxygenase-2: Expression and risk of gastric cancer and its precursors in a Chinese population.
OBJECTIVE
To screen the genetic variants in cyclooxygenase-2 (COX-2), and evaluate their effects on COX-2 expression and risk of gastric cancer (GC) and its precursors, a population-based study was conducted in Linqu County, Shangdong Province, an area of China, a high-risk area of GC.


METHODS
Genotypes were determined by polymerase chain reaction (PCR)-based denaturing high-performance liquid chromatography analysis in 248 GC cases and 1523 subjects with precancerous gastric lesions. COX-2 expression was detected by immunohistochemical analysis of biopsy specimens of 593 subjects selected at random from 1523 subjects. COX-2 transcriptional activity was examined by luciferase reporter gene assay.


RESULTS
We found an increased risk of GC in subjects with -1195 AA genotype (adjusted odds ratio [OR], 2.33; 95% confidence interval [CI]: 1.45-3.75). Stratified analysis indicated that an elevated risk of GC was observed in subjects carrying the AA genotype and Helicobacter pylori infection (OR, 3.88; 95% CI: 1.46-10.34) or smoking (OR, 7.02; 95% CI: 2.19-22.48), and a high expression of COX-2 was found in subjects with AA genotype (OR, 1.84; 95% CI: 1.09-3.10) compared with GG genotype. The prevalence of COX-2 expression positivity varied markedly by histologic status, and the OR (OR, 5.35; 95% CI: 2.64-10.8) was significantly increased for dysplasia compared with superficial gastritis/chronic atrophic gastritis. Furthermore, tissue homogenate with H pylori infection could significantly stimulate COX-2 promoter activity driven by -1195A compared with the -1195G containing counterparts.


CONCLUSIONS
These findings suggest that COX-2 polymorphisms may play an important role, at least in part, in developing GC in this high-risk population.
Liu
Fen
F
Department of Cancer Epidemiology, Peking University School of Oncology, Beijing Institute for Cancer Research, Beijing Cancer Hospital, Beijing, China.
Pan
Kaifeng
K
Zhang
Xuemei
X
Zhang
Yang
Y
Zhang
Lian
L
Ma
Junling
J
Dong
Caixuan
C
Shen
Lin
L
Li
Jiyou
J
Deng
Dajun
D
Lin
Dongxin
D
You
Weicheng
W
D000328:Adult; D017677:Age Distribution; D001483:Base Sequence; D002681:China / Q000453:epidemiology; D016001:Confidence Intervals; D003430:Cross-Sectional Studies; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005820:Genetic Testing; D014644:Genetic Variation; D005838:Genotype; D016481:Helicobacter Infections / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology; D015995:Prevalence; D018570:Risk Assessment; D017678:Sex Distribution; D013274:Stomach Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology
D051546:Cyclooxygenase 2