遗传变异与幽门螺杆菌感染在胃癌发生中的交互作用

Interaction between genetic variation and Helicobacter pylori infection in the occurrence of gastric cancer

目的探讨胃癌已知易感遗传变异与幽门螺杆菌(Helicobacter pylori,H.pylori)在胃癌发生中的交互作用,及其对胃癌发生部位和发病年龄的影响。方法采用单纯病例研究设计,在2426例胃癌患者中,通过二元Logistic回归分析模型分析遗传变异与H.pylori之间的交互作用。结果调整混杂因素后发现,遗传变异NSUN 3 rs7624041和DEFB rs2376549与H.pylori感染在胃癌发生中交互作用有统计学意义(OR=1.257,95%CI:1.006~1.571,P=0.044;OR=0.845,95%CI:0.715~0.999,P=0.048)。基于肿瘤部位的分层分析发现,遗传变异与H.pylori感染之间不存在交互作用。基于肿瘤TNM(tumor-node-metastasis)分期的分层分析发现,在TNM早期胃癌患者中,遗传变异lnc-POLR3G-4 rs7712641与H.pylori感染交互作用有统计学意义(OR=1.757,95%CI:1.060~2.915,P=0.029)。基于年龄的分层分析发现,在年龄<60岁人群中,ASHIL rs80142782、NSUN 3 rs7624041和DEFB rs2376549与H.pylori感染交互作用有统计学意义(OR=1.602,95%CI:1.006~2.551,P=0.047;OR=1.811,95%CI:1.247~2.632,P=0.002;OR=0.688,95%CI:0.520~0.910,P=0.009);而在年龄≥60岁人群中,仅有PSCA rs2294008和CUX 2 rs6490061与H.pylori感染交互作用有统计学意义(OR=0.775,95%CI:0.630~0.954,P=0.016;OR=0.790,95%CI:0.635~0.982,P=0.034)。结论胃癌的发生发展较为复杂,通过整合遗传因素和环境因素,针对易感高危人群采取H.pylori的根除措施,将有助于预防胃癌的发生发展。

Objective To investigate the interaction between known genetic variation of gastric cancer and Helicobacter pylori(H.pylori)in the occurrence of gastric cancer,and its effect on tumor site and the age at onset of gastric cancer.Methods With a case-only design,the interaction between genetic variation and H.pylori was analyzed by binary Logistic regression analysis in 2426 patients with gastric cancer.Results After adjusting confounding factors,the interactions of genetic variation NSUN 3 rs7624041 and DEFB rs 2376549 with H.pylori infection in gastric cancer were statistically significant(OR=1.257,95%CI:1.006-1.571,P=0.044;OR=0.845,95%CI:0.715-0.999,P=0.048).Based on the hierarchical analysis of tumor location,there was no interaction between genetic variation and H.pylori infection.Hierarchical analysis based on tumor stage showed that the interaction between lnc-POLR3G-4 rs7712641 and H.pylori infection was statistically significant in patient with early gastric cancer(OR=1.757,95%CI:1.060-2.915,P=0.029).The age-based stratified analysis results showed that the interactions between ASHIL rs80142782,NSUN 3 rs7624041,DEFB rs2376549 and H.pylori infection were statistically significant in people aged<60 years(OR=1.602,95%CI:1.006-2.551,P=0.047;OR=1.811,95%CI:1.247-2.632,P=0.002;OR=0.688,95%CI:0.520-0.910,P=0.009).And the interactions between PSCA rs2294008,CUX 2 rs6490061 and H.pylori infection were statistically significant in people over 60 years old(OR=0.775,95%CI:0.630-0.954,P=0.016;OR=0.790,95%CI:0.635-0.982,P=0.034).Conclusions The occurrence and development of gastric cancer is complex.It is helpful to prevent the occurrence and development of gastric cancer by integrating genetic factors and environmental factors and taking targeted H.pylori eradication measures for susceptible and high-risk groups.