肿瘤坏死因子β基因多态性与胃癌遗传易感性的关联  

Association between tumor necrosis factor-βgene polymorphisms and genetic predisposition to gastric cancer

作　　者：谢素红 胡宏峰 郑慧 卢仁泉 郭林 Xie Suhong;Hu Hongfeng;Zheng Hui;Lu Renquan;Guo Lin(Department of Clinical Laboratory,Fudan University Shanghai Cancer Center,Department of Oncology,Shanghai Medical College,Fudan University,Shanghai200032,China)

机构地区：[1]复旦大学附属肿瘤医院检验科,复旦大学上海医学院肿瘤学系,上海200032

出　　处：《中华检验医学杂志》2024年第11期1264-1270,共7页Chinese Journal of Laboratory Medicine

基　　金：国家自然科学基金(82072876)。

摘　　要：目的探讨肿瘤坏死因子β(TNF-β)基因多态性与胃癌易感性的关系,同时分析TNF-β特定基因型与血清TNF-β表达水平之间的联系。方法采用病例对照的研究方法,选取2021年9月至2022年12月在复旦大学附属肿瘤医院确诊为胃癌的患者153例为胃癌组;选取同期健康体检者150名为健康对照组。研究前期利用常规PCR扩增检测胃癌组和对照组外周血DNA各30份,经测序鉴定TNF-β多态性位点(rs1041981、rs2229092、rs2229094和rs78613290)的基因型频率;后续利用等位基因特异性荧光定量PCR法进一步检测分析TNF-β多态性位点的基因型与等位基因频率;用酶联免疫吸附法(ELISA)测定血清TNF-β水平,并分析与TNF-β特定基因型的关系。采用χ^(2)检验和Fisher检验分析TNF-β多态性位点的基因型分布频率,采用非参数统计分析血清TNF-β表达水平差异。结果30例胃癌患者和30名健康对照测序结果显示,多态性位点rs1041981在胃癌组的基因型分布是CC型16.67%(5/30)、CA型40.00%(12/30)和AA型43.33%(13/30),在对照组的基因型分布是CC型40.00%(12/30)、CA型43.33%(13/30)和AA型16.67%(5/30),基因型频率差异有统计学意义(χ^(2)=6.478,P=0.039);多态性位点rs2229092在2组的基因型为AA、AG和GG,分布频率差异无统计学意义(χ^(2)=1.888,P=0.612);多态性位点rs2229094基因型(TT和TC)和rs78613290基因型(GG和AG)在2组的分布频率差异无统计学意义(P均>0.05)。进一步扩大临床样本(胃癌组153例,对照组150例)验证发现,胃癌组位点rs1041981基因型[CC型15.69%(24/153)、CA型54.90%(84/153)、AA型29.4%(45/153)]与对照组[CC型27.33%(41/150)、CA型58.00%(87/150)、AA型14.67%(22/150)]的分布频率差异有统计学意义(χ^(2)=12.366,P=0.002),分析不同等位基因频率对于胃癌风险的影响,发现rs1041981的A等位基因发生胃癌的风险相对于C等位基因比值比(OR)为1.701(95%CI 1.235~2.355)。结合胃癌患者的临床病理特征进行基因表型�Objective To investigate the association between tumor necrosis factor-β(TNF-β)gene polymorphisms and genetic predisposition to gastric cancer,and to analyze the relationship between specific genotype of TNF-βand serum levels of TNF-β.Methods Using case control study,we selected 153 patients with gastric cancer in Fudan University Shanghai Cancer Center between September 2021 and December 2022 as the gastric cancer group,and 150 healthy individuals were chosen as the healthy control group.In the previous study,30 peripheral blood DNA samples of gastric cancer patients and healthy controls respectively were amplified by conventional PCR,which were sequenced to identify the genotype frequencies of TNF-βpolymorphic loci(rs1041981,rs2229092,rs2229094 and rs78613290);consequently,Allele-Specific Quantitative PCR was used to further detect and analyze the genotype and genotype frequencies of TNF-βpolymorphic loci;serum TNF-βlevels were measured by Enzyme-Linked Immunosorbent Assay(ELISA),and the relationship with specific genotypes of TNF-βwas analyzed.Chi-square test and Fisher test were used to analyze the genotype distribution frequency of TNF-βpolymorphic loci,and non-parametric statistics was used to analyze the differences in serum TNF-βexpression levels.Results The sequencing results showed that the genotype distribution of rs1041981 in gastric cancer group was CC 16.67%(5/30),CA 40.00%(12/30)and AA 43.33%(13/30).The genotype distribution in control group was CC 40.0%(12/30),CA 43.33%(13/30),AA 16.7%(5/30).The difference of genotype frequency between the two groups was statistically significant(χ^(2)=6.478,P=0.039).The genotypes of the polymorphic loci rs2229092 in both groups were AA,AG,and GG,with no statistically significant difference between the two groups(χ^(2)=1.888,P=0.612).The distribution frequencies of the genotypes of the polymorphic loci rs2229094(TT and TC)and rs78613290(GG and AG)showed no statistically significant differences between the two groups(both P>0.05).Further validation with

关 键 词：肿瘤坏死因子 胃癌 单核苷酸多态性 易感性 

分 类 号：R735.2[医药卫生—肿瘤]