COX-2、PARP-1基因多态性与回族人群胃癌易感性的关联研究
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摘要
目的探讨环氧化酶-2(COX-2)-765G＞C和聚腺苷二磷酸核糖聚合酶-1(PARP-1)Val762Ala(2444T/C)的两个单核苷酸多态与回族人群胃癌易感性的关系。
方法以PCR-限制性片段长度多态性方法对回族人群中100例胃癌组、102例癌前病变组和105例正常对照组进行基因分型。使用ELISA法检测H.pylori感染。用SPSS13.0统计软件分析试验结果。
结果三组中的二个SNPS的基因型频率分布均符合Hardy-Wenibegr遗传平衡定律。COX-2-765 GC+CC基因型在胃癌组显著增高,OR值为1.977(95%Cl:1.104～3.541,P=0.021);PARP-12444TC+CC基因型在胃癌组显著增高,OR值为1.898(95%Cl:1.030～3.500,P=0.039)。分层分析显示:在H.pylori感染阳性人群中,-765C携带者患胃癌的风险是-765 GG携带者的2.121倍(OR:2.121,95%Cl:1.000～4.498,P=0.048);2444C携带者患胃癌的风险是2444TT携带者的2.270倍(OR:2.270,95%Cl:1.023～5.037,P=0.042)。交互作用分析显示:家族史阳性的-765GC+CC携带者患胃癌的风险是家族史阴性的-765GG基因型携带者的3.738倍(OR:3.738,95%Cl:1.451～9.628,P=0.005);食腌菜的-765GC+CC基因型患胃癌的风险是不食腌菜的-765GG基因型的5.038倍(OR:5.038,95%Cl:2.261～11.224,P=0.000),食腌菜的2444TC+CC携带者患胃癌的风险是不食腌菜的2444TT携带者的3.408倍(OR:3.408,95%Cl:1.505～7.714,P=0.003);H.pylori感染阳性的-765GC+CC携带者患胃癌的风险是HP感染阴性-765 GG携带者的3.520倍(OR:3.520,95%Cl:1.579～7.850,P=0.002),HP感染阳性的2444TC+CC携带者患胃癌的风险是H.pylori感染阴性的2444TT携带者的2.889倍(OR:2.889,95%Cl:1.265～6.598,P=0.010)。同时为-765 C和2444C携带者患胃癌的发病风险是同时为-765GG和2444TT携带者的3.771倍(OR,3.771;95%Cl,1.429-9.947;P=0.021)。
结论COX-2-765G＞C和PARP-1 Val762Ala(2444T/C)两个单核苷酸多态与中国甘肃地区回族人群胃癌易感性增高相关。-765 GC+CC与家族史,-765 GC+CC、2444TC+CC与食腌菜,-765GC+CC、2444TC+CC与H.pylori感染,-765GC+CC和2444TC+CC在胃癌的发病风险中存在着明显的加乘交互效应。
Objective To explore the correlation of nucleotide polymorphisms in cyclooxygenase-2(COX-2) -765G＞C,poly(ADP-ribose)polymerase-1 (PARP-1) Va1762Ala(T2444C) and the susceptibility to gastric cancer in Hui ethnic group.
Methods All investigated objects were divided into 3 groups:100 gastric cancer patients,102 precancerous lesion patients and 105 control subjects were enrolled.Polymerase chain reaction-restrieted fragments length polymorphism(PCR-RFLP) method was used to defect genotypes of -765G＞C and 2444 T/C polymorphisms.ELASA method was used to identify IgG to H.pylori.The results were analyzed by SPSS13.0.
Result COX-2-765GC+CC genotypes were overrepresented in GC(the gastric cancer group)(43.0%) compared with controls(27.6%)(OR,1.977, 95%C1:1.104～3.541,P=0.021).PARP-12444TC+CC genotypes were overrepresented in GC(36.0%) compared with controls(22.8%)(OR,1.898; 95%Cl,1.030～3.500,P=0.039).Stratification analysis showed that:among group with positive HP infection,-765GC+CC carriers could increased the susceptibility to gastric cancer compared with -765GG carriers(OR:2.121, 95%CI:1.000～4.498,P=0.048)and 2444TC+CC carriers could increased the susceptibility to gastric cancer compared with 2444TT carriers(OR: 2.270,95%Cl:1.023～5.037,P=0.042).Interaction analysis showed that: -765GC+CC carriers with Positive family history of GC had 3.738 fold increased risk for developing gastric cancer compared with -765GG carriers with negative family history of GC(OR:3.738,95%Cl:1.451～9.628, P=0.005);-765 GC+CC carriers with eating pickle vegetables had 5.038 fold increased risk for developing gastric cancer compared with -765GG carriers with not- eating pickle vegetables(OR:5.038,95%Cl:2.261～11.224, P=0.000);2444TC+CC carriers with eating pickle vegetables had 3.408 fold increased risk for developing gastric cancer compared with 2444TT carriers with not-eating pickle vegetables(OR:3.408,95%Cl:1.505～7.714, P=0.003).-765 GC+CC carriers with positive H.pylori infection had 3.520 fold increased risk for developing gastric cancer compared with -765 GG carriers with negative H.pylori infection(OR:3.520,95%Cl.1.579～7.850,P=0.002); 2444TC+CC carriers with positive H.pylori infection had 2.889 fold increased risk for developing gastric cancer compared with 2444TT carriers with negative Hp infection(OR:2.889,95%Cl,1.265～6.598,P=0.010).The subjects simultaneously carrying -765 GC+CC and 2444TC+CC genotypes had 3.771 fold increased risk for developing gastric cancer compared with subjects simultaneously carryng -765 GG and 2444TT(OR,3.771;95%Cl, 1.429-9.947;P=0.021).
Conclusion COX-2-765G＞C and PARP-1Va1762Ala(2444T/C) contributed to the increased susceptibility to gastric cancer in Hui ethnic group in Linxia City,Gansu Province.Multiplicative interactions lied in between COX-2-765 GC+CC and positive family history of GC,-765 GC+CC、2444TC+CC and eating pickle vegetables,-765 GC+CC、2444TC+CC and H.pylori infection,-765GC+CC and 2444TC+CC in risk of developing gastric cancer.
方法以PCR-限制性片段长度多态性方法对回族人群中100例胃癌组、102例癌前病变组和105例正常对照组进行基因分型。使用ELISA法检测H.pylori感染。用SPSS13.0统计软件分析试验结果。
结果三组中的二个SNPS的基因型频率分布均符合Hardy-Wenibegr遗传平衡定律。COX-2-765 GC+CC基因型在胃癌组显著增高,OR值为1.977(95%Cl:1.104～3.541,P=0.021);PARP-12444TC+CC基因型在胃癌组显著增高,OR值为1.898(95%Cl:1.030～3.500,P=0.039)。分层分析显示:在H.pylori感染阳性人群中,-765C携带者患胃癌的风险是-765 GG携带者的2.121倍(OR:2.121,95%Cl:1.000～4.498,P=0.048);2444C携带者患胃癌的风险是2444TT携带者的2.270倍(OR:2.270,95%Cl:1.023～5.037,P=0.042)。交互作用分析显示:家族史阳性的-765GC+CC携带者患胃癌的风险是家族史阴性的-765GG基因型携带者的3.738倍(OR:3.738,95%Cl:1.451～9.628,P=0.005);食腌菜的-765GC+CC基因型患胃癌的风险是不食腌菜的-765GG基因型的5.038倍(OR:5.038,95%Cl:2.261～11.224,P=0.000),食腌菜的2444TC+CC携带者患胃癌的风险是不食腌菜的2444TT携带者的3.408倍(OR:3.408,95%Cl:1.505～7.714,P=0.003);H.pylori感染阳性的-765GC+CC携带者患胃癌的风险是HP感染阴性-765 GG携带者的3.520倍(OR:3.520,95%Cl:1.579～7.850,P=0.002),HP感染阳性的2444TC+CC携带者患胃癌的风险是H.pylori感染阴性的2444TT携带者的2.889倍(OR:2.889,95%Cl:1.265～6.598,P=0.010)。同时为-765 C和2444C携带者患胃癌的发病风险是同时为-765GG和2444TT携带者的3.771倍(OR,3.771;95%Cl,1.429-9.947;P=0.021)。
结论COX-2-765G＞C和PARP-1 Val762Ala(2444T/C)两个单核苷酸多态与中国甘肃地区回族人群胃癌易感性增高相关。-765 GC+CC与家族史,-765 GC+CC、2444TC+CC与食腌菜,-765GC+CC、2444TC+CC与H.pylori感染,-765GC+CC和2444TC+CC在胃癌的发病风险中存在着明显的加乘交互效应。
Objective To explore the correlation of nucleotide polymorphisms in cyclooxygenase-2(COX-2) -765G＞C,poly(ADP-ribose)polymerase-1 (PARP-1) Va1762Ala(T2444C) and the susceptibility to gastric cancer in Hui ethnic group.
Methods All investigated objects were divided into 3 groups:100 gastric cancer patients,102 precancerous lesion patients and 105 control subjects were enrolled.Polymerase chain reaction-restrieted fragments length polymorphism(PCR-RFLP) method was used to defect genotypes of -765G＞C and 2444 T/C polymorphisms.ELASA method was used to identify IgG to H.pylori.The results were analyzed by SPSS13.0.
Result COX-2-765GC+CC genotypes were overrepresented in GC(the gastric cancer group)(43.0%) compared with controls(27.6%)(OR,1.977, 95%C1:1.104～3.541,P=0.021).PARP-12444TC+CC genotypes were overrepresented in GC(36.0%) compared with controls(22.8%)(OR,1.898; 95%Cl,1.030～3.500,P=0.039).Stratification analysis showed that:among group with positive HP infection,-765GC+CC carriers could increased the susceptibility to gastric cancer compared with -765GG carriers(OR:2.121, 95%CI:1.000～4.498,P=0.048)and 2444TC+CC carriers could increased the susceptibility to gastric cancer compared with 2444TT carriers(OR: 2.270,95%Cl:1.023～5.037,P=0.042).Interaction analysis showed that: -765GC+CC carriers with Positive family history of GC had 3.738 fold increased risk for developing gastric cancer compared with -765GG carriers with negative family history of GC(OR:3.738,95%Cl:1.451～9.628, P=0.005);-765 GC+CC carriers with eating pickle vegetables had 5.038 fold increased risk for developing gastric cancer compared with -765GG carriers with not- eating pickle vegetables(OR:5.038,95%Cl:2.261～11.224, P=0.000);2444TC+CC carriers with eating pickle vegetables had 3.408 fold increased risk for developing gastric cancer compared with 2444TT carriers with not-eating pickle vegetables(OR:3.408,95%Cl:1.505～7.714, P=0.003).-765 GC+CC carriers with positive H.pylori infection had 3.520 fold increased risk for developing gastric cancer compared with -765 GG carriers with negative H.pylori infection(OR:3.520,95%Cl.1.579～7.850,P=0.002); 2444TC+CC carriers with positive H.pylori infection had 2.889 fold increased risk for developing gastric cancer compared with 2444TT carriers with negative Hp infection(OR:2.889,95%Cl,1.265～6.598,P=0.010).The subjects simultaneously carrying -765 GC+CC and 2444TC+CC genotypes had 3.771 fold increased risk for developing gastric cancer compared with subjects simultaneously carryng -765 GG and 2444TT(OR,3.771;95%Cl, 1.429-9.947;P=0.021).
Conclusion COX-2-765G＞C and PARP-1Va1762Ala(2444T/C) contributed to the increased susceptibility to gastric cancer in Hui ethnic group in Linxia City,Gansu Province.Multiplicative interactions lied in between COX-2-765 GC+CC and positive family history of GC,-765 GC+CC、2444TC+CC and eating pickle vegetables,-765 GC+CC、2444TC+CC and H.pylori infection,-765GC+CC and 2444TC+CC in risk of developing gastric cancer.
引文
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