环氧化酶2启动子区遗传变异及其与胃癌发病风险的关系

目的筛查环氧化酶2(COX-2)启动子区遗传变异并探讨其与胃癌发病风险的关系。方法以单链构象多态及测序的方法筛查COX-2启动子区遗传变异,以PCR-限制性片断长度多态性方法对筛查到的变异在323例胃癌患者和646名健康对照中进行基因分型。以logistic回归计算比值比(OR)及其95%可信区限(CI)。单体型由Haplo·stat软件构建。结果筛查到COX-2启动子区3个单核苷酸变异,即-1290A>G、-1195G>A和-765G>C。-1290AG、-1195AA和-765CG基因型与胃癌风险增高相关,OR分别为1·64(95%CI1·03~2·61)、2·68(95%CI1·65~4·33)和2·66(95%CI1·53~4·64)。单体型分析结果显示,与A-1290-G-1195-G-765单体型比较,A-1290-A-1195-C-765单体型发生胃癌的风险较高,OR为11·80(95%CI2·43~57·25)。结论COX-2启动子区遗传变异与胃癌易感性相关。

Genetic polymorphisms in the promoter region of cyclooxygenase-2 and their association with risk of gastric cancer

OBJECTIVE: To examine the genetic polymorphisms in the promoter region of cyclooxygenase-2 ( COX-2) and evaluate their association with the risk of gastric cancer. METHODS: Single-strand conformational polymorphism and DNA sequencing were used to screen the genetic variants of the COX-2 promoter region. Total 323 patients with gastric cancer and 646 frequency-matched controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism method. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression. Haplotype frequency was estimated using Haplo. stat software. RESULTS: Three single nucleotide polymorphisms, including - 1290A > G, -1195G > A, and -765G > C were identified in the promoter of COX- 2. Case-control analysis showed an increased risk of developing gastric cancer for the -1290AG (OR 1.64; 95% CI 1.03-2.61), -1195AA (OR 2.68; 95% CI 1.65-4.33), and -765CG (OR 2.66; 95% CI 1.53-4.64) genotype carriers, respectively, compared with noncarriers. A greater risk of developing gastric cancer was observed for the A(-1290) -A(-1195) -C(-765) haplotype compared with the A(-1290) -G(-1195) -G(-765) haplotypes (OR 11.80; 95% CI 2.43-57.25). CONCLUSION: Genetic polymorphisms in COX-2 promoter region may play a role in gastric carcinogenesis.