PPAR-γ2基因-C34G、NADPH氧化酶p22phox亚基基因-C242T多态性与幽门螺杆菌感染的交互作用和食管鳞状细胞癌的关系

摘要

Objective To investigate the interaction of polymorphisms of PPAR-γ2 gene-C34G and NADPH oxidase subunit p22phox gene-C242T with helicobacter pylori (H.pylori) infection in esophageal squamous cell carcinoma (ESCC).Methods A total of 200 cases of LSCC of Broder grade Ⅰ,200 of Broder grade Ⅱ and of grade Ⅲ were enrolled in this study with 200 healthy individuals as the control group.The genetic polymorphisms of PPAR-γ2 gene-C34G and NADPH oxidase subunit p22phox gene-C242T were analyzed using PCR-RFLP in peripheral blood leukocytes.14C-urea breath test (14C-UBT) was used to test 14C disntegration per minute (DPM) for evaluating the infection status of H.pylori.An unconditional logistic regression model was used to analyze the interaction of nucleotide polymorphisms and H.pylori infection.Results The risk of ESCC significantly increased in subjects with-C34G (CG),-C34G(GG),-C242T (CT),and-C242T (TT) genotypes.Combined analysis of the polymorphisms showed that the subjects carrying-C34G (GG)/-C242T (TT) had a high risk of ESCC,and a positive interaction was found between-C34G (GG) and-C242T (TT) in increasing the risk of ESCC.Positive interactions in the pathogenesis of ESCC were also found between-C34G (CG) and-C242T (TT),between-C34G (CG) and-C242T (CT),and between-C34G (GG) and-C242T (CT) (γ＞1).The risk of ESCC significantly increased in subjects with H.pyloriinfection,which showed positive interactions with-C34G (CG),-C34G (GG),-C242T (CT) and-C242T (TT) in increasing the risk of ESCC (γ＞1).Conclusion Individuals carrying-C34G(CG),-C34G(GG),-C242T (CT) and-C242T (TT) genotypes have a high risk of developing ESCC,and these genotypes interact with H.pylori infection in the pathogenesis of LSCC,suggesting the importance of eradicating H.pylorifor prevention of ESCC.%目的 探讨过氧化物酶体增殖因子活化受体-γ2 (PPAR-γ2)基因-C34G、烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶p22phox亚基基因-C242T多态性与幽门螺杆菌(H.Pylori)感染的交互作用和食管鳞状细胞癌(ESCC)的关系.方法 选择我院2010年5月～2015年3月收治的ESCCBroder Ⅰ级、BroderⅡ级和BroderⅢ级患者各200例,以200例健康体检者作为对照组,以上述各组患者的外周血白细胞为样本,利用PCR-RFLP检测PPAR-γ2基因-C34G和NADPH氧化酶p22phox亚基基因-C242T多态性.采用14C-UBT检测受检者H.Pylori与14C结合的每分钟衰变数(DPM)以判断H.Pylori感染情况.采用非条件Logistic回归对-C34G、-C242T多态性与H.Pylori感染的交互作用进行分析.结果-C34G(CG)和-C34G(GG)基因型者患ESCC的风险均显著增加,-C242T(CT)和-C242T(TT)基因型者患ESCC的风险也显著增加.基因突变的协同分析发现-C34G(GG)和-C242T(TT)基因型在ESCC发生、发展存在正向的交互作用,另外在-C34G (CG)和-C242T(TT)之间、-C34G(CG)和-C242T(CT)之间及-C34G(GG)和-C242T (CT)之间均存在正向交互作用(γ均大于1).H.Pylori感染者患ESCC的风险性均明显增高.H.Plylori感染与-C34G(CG)、-C34G(GG)、-C242T(CT)和-C242T(TT)基因型与均有正向交互作用(γ均大于1).结论 携带-C34G(CG)、-C34G(GG)、-C242T(CT)和-C242T(TT)基因型的个体属ESCC高危险人群,这些基因型和H.Pylori感染的交互作用促进了ESCC的发生、发展,应当采取根除H.Pylori或调控基因表达的措施以达到有效预防LSCC的目的.