环氧化酶23'非翻译区+8473T>C基因多态性及其与吸烟、幽门螺杆菌感染的交互作用对食管癌发病的影响研究

Influence of Cyclooxygenase 2 3′Untranslated Regions Genetic Polymorphism and Interaction with Smoking and Helicobacter Pylori Infection on the Invasion of Esophageal Cancer

目的探讨环氧化酶2(COX-2)3'非翻译区(3'UTR)+8473T>C基因多态性及其与吸烟、幽门螺杆菌感染的交互作用对食管癌发病的影响。方法选择2006年1月—2011年1月在唐山市工人医院进行治疗的食管癌患者119例为病例组,按照2∶1比例选择同期体检正常者238例为对照组。采用聚合酶链反应-限制性片段长度多态性技术进行基因分型;采用非条件Logistic回归模型进行分析,计算OR值及其95%CI。结果病例组携带1个C等位基因、2个C等位基因、TC+CC基因型者的食管癌发病风险分别为对照组的1.60倍〔95%CI(0.91,2.83),P=0.08〕、3.29倍〔95%CI(1.10,11.62),P=0.03〕、1.76倍〔95%CI(1.12,2.93),P=0.02〕。在吸烟人群中,病例组携带COX-2 3'UTR+8473C等位基因者食管癌发病风险是对照组的2.11倍〔95%CI(1.08,3.96),P=0.02〕;在血清幽门螺杆菌抗体阳性人群中,病例组携带COX-2 3'UTR+8473C等位基因者食管癌发病风险是对照组的3.98倍〔95%CI(1.85,8.46),P<0.001〕。结论 COX-2 3'UTR+8473T>C基因多态性是影响食管癌发病的重要的遗传易患因素,可增加食管癌发病风险,且与吸烟、幽门螺杆菌存在交互作用。

Objective To explore the influence of cyclooxygenase 2 3＇untranslated regions （ COX - 2 3＇UTR） genetic polymorphism and interaction with smoking and Helicobacter pylori （ H. pylori） infection on the invasion of esophageal canc- er. Methods A total of 119 patients with esophageal cancer treated in Worker＇s Hospital of Tangshan from Jan 2006 to Jan 2011 were selected as the case group. A total of 238 healthy subjects were selected as control group who did health examination at ratio of 2：1 in the same time. The two groups were genotyped by polymerase chain reaction - restriction fragment length polymorphism method. Odds ratios （OR） and 95% confidence intervals （CI） were estimated by Logistic regression. Results Case - control analysis showed an increased risk of developing esophageal cancer for one C allele [ OR = 1.60, 95% CI （0. 91, 2. 83 ）, P = 0.083 carriers, ＋8473 CC [0R=3.29, 95%CI （1.10, 11.62）, P=0.03] genotype carriers and ＋8473 TC ＋CC geno- type [ OR = 1.76, 95 % CI （ 1.12, 2. 93 ）, P = 0. 02 ], compared with control group. When stratified by H. pylori infection sta- tus, the significant increased risk of esophageal cancer was found among H. pylori carrier with COX -2 3 ＇UTR ＋ 8473C allele （ OR = 3.98, 95% CI （ 1.85, 8.46）, P 〈 0. 001 ], but not among H. pylori non - carriers. When stratified by smoking status, the significant increased risk of esophageal cancer was found among smokers [ OR =2. 11, 95% CI （ 1.08, 3.96） 3, but not a- mong non - smokers. Conclusion Genetic polymorphism in COX - 2 3＇UTR interacting with smoking and H. pylori infection plays an important role in the development of esophageal cancer.