CYP1A1、GSTM1及GSTT1基因多态性与原发性肝癌遗传易感性的关联研究  

Associations of CYP1A1,GSTM1 and GSTT1 gene polymorphisms with susceptibility to primary hepatocellular carcinoma

作　　者：罗小虎[1] 朱硕 曹生亚[1] LUO Xiao-Hu;ZHU Shuo;CAO Sheng-Ya(Xuzhou Cancer Hospital,Jiangsu Xuzhou 221000,China)

机构地区：[1]徐州市肿瘤医院,江苏徐州221000

出　　处：《江苏预防医学》2023年第3期281-284,共4页Jiangsu Journal of Preventive Medicine

基　　金：2018年度第二批徐州市医学重点学科建设项目(2018XJ-2);徐州市卫生健康委科技项目(XWKYHT20210573)。

摘　　要：目的 探讨细胞色素P450酶1A1(CYP1A1)基因rs1048943位点、谷胱甘肽S转移酶M1(GSTM1)基因和谷胱甘肽S转移酶T1(GSTT1)基因单核苷酸多态性与原发性肝癌(Hepatocellular carcinoma, HCC)易感性的关系。方法 采用病例对照方法,选择徐州市肿瘤医院确诊的100例原发性肝癌患者作为病例组,按(年龄±5)岁,同性别1∶1配对健康人群作为对照组。应用多重PCR技术对两组人群进行CYP1A1基因rs1048943位点多态性、GSTM1及GSTT1基因缺失检测,以交互作用相对超额危险度(RERI)、交互作用归因比(AP)和交互作用指数(SI)对相加交互作用进行定量描述。结果 相对于对照组,病例组CYP1A1携带AG、GG基因型患者患肝癌的风险为3.90、16.00倍;GSTM1和GSTT1基因纯合缺失患者患肝癌风险为3.27、2.92倍。叉生分析发现,以CYP1A1/AA+GSTM1(II)或GSTT1(II)作为阴性暴露,CYP1A1 AG+GG联合GSTM1纯合缺失患者风险为28.27倍,CYP1A1 AG+GG基因型联合GSTT1纯合缺失患者风险为11.08倍。与CYP1A1携带AA的不饮酒个体相比,携带AG+GG的饮酒个体肝癌风险增加:RERI为1.92(1.21~4.12),AP为0.21(0.01~0.72),SI为1.12(1.04~3.99),两者具有相加交互作用。结论 CYP1A1基因突变以及GSTM1、GSTT1纯合缺失是原发性肝癌的遗传易感因素,两者联合作用可增加患肝癌风险;饮酒与CYP1A1基因突变存在相加交互作用,两者结合亦可增加患肝癌风险。Objective To examine the associations of cytochrome P450 family 1 subfamily A member 1(CYP1A1)rs1048943 variant,glutathione S⁃transferase mu 1(GSTM1)and glutathione S⁃transferase Theta 1(GSTT1)polymorphisms with susceptibility to primary hepatocellular carcinoma(HCC).Methods A case⁃control study was performed.One hundred patients with definitive diag⁃nosis of primary HCC in Xuzhou Cancer Hospital served as the case group,while 1:1 matched healthy individuals of the same gender within 5 years above and below served as the control group.The CYP1A1 rs1048943 polymorphism,and GSTM1 and GSTT1 gene dele⁃tions were among subjects in both groups detected using multiplex PCR assay,and the additive interactions were quantitatively measured using the relative excess risk due to interaction(RERI),attributable proportion due to interaction(AP)and synergy index(SI).Results Participants carrying the AG and GG genotypes of the CYP1A1 gene were 3.90 and 16.00 times more likely to devel⁃op primary HCC in the case group than in the control group,while subjects carrying GSTM1 and GSTT1 gene deletions were 3.27 and 2.92 times more likely to develop primary HCC in the case group than in the control group.Crossover analysis showed that individuals with CYP1A1 AG+GG combined GSTM1 homozygous deletion had a 28.27 times higher risk of primary HCC if CYP1A1/AA+GSTM1(II)or GSTT1(II)served as negative exposure.Individuals carrying CYP1A1 AG+GG and with alcohol consumption had an increased risk of primary HCC relative to individuals carrying CYP1A1 AA genotype and without alcohol consumption[RERI=1.92,95%CI:(1.21,4.12);AP=0.21,95%CI:(0.01,0.72);SI=1.12,95%CI:(1.04,3.99)],and there was additive interaction be⁃tween CYP1A1 mutation and alcohol consumption.Conclusions CYP1A1 gene mutation and GSTM1 and GSTT1 homozygous deletions are genetic factors contributing to primary HCC susceptibility,and the combination of CYP1A1 mutation and GSTM1 and GSTT1 homozygous deletions may increase the risk of HCC.There is additive interaction betw

关 键 词：CYP1A1 GSTM1 GSTT1 原发性肝癌 基因多态性 

分 类 号：R735.7[医药卫生—肿瘤]