JAK／STAT信号通路中关键分子基因多态性与肝细胞癌易感性的关系  

Association of genetic polymorphisms of key molecules in JAK/STAT signaling pathway with susceptibility of hepatocellular carcinoma

作　　者：谢佳新[1] 殷建华[1] 张琪[1] 蒲蕊[1] 张玉伟[1] 鹿文英[1] 曹广文[1] 

机构地区：[1]第二军医大学流行病学教研室,上海200433

出　　处：《中华流行病学杂志》2012年第2期215-219,共5页Chinese Journal of Epidemiology

基　　金：基金项目：国家自然科学基金（81025015,30901272,30921006）;上海市自然科学基金（09ZR1439200）

摘　　要：目的探讨宿主JAK／STAT信号通路中关键分子基因多态性与肝细胞癌（HCC）易感性的关系。方法采用病例对照研究，用质谱法对367例诊断明确的HBsAg阳性HCC患者（HCC组）和性别、年龄匹配的367例对照的IL-6（rs1800796，-572C〉G）、STAT3（rs744166，426312T〉C；rs3816769，＋42240T〉C；rs6503695，＋40980T〉C）、EGFR（rs11543848，＋142530A〉G）、mTOR（rs7211818，＋170278A〉G；rs9674559，＋196983A〉G；rs11653499，＋65678G〉A）进行多态性检测。单因素分析确定各位点多态性比值比（OR）和95％可信区问（凹）。结果IL-6、STAT3、EGFR、mTOR的8个多态性位点各基因型在HCC组和对照组中分布的差异无统计学意义（P〉0．05）。按性别分层后，在女性中，与TT基因型相比，携带STAT3＋26312CC、＋42240CC、十40980CC基因型个体患HCC的危险陛降低（OR=0．192，95％CI=0．047～0．784；OR=0．180，95％CI：0．045～0．725；OR=0．198，95％CI：0．049～0．806）。与AA基因型相比，EGFR＋142530（AG＋GG）基因型降低女性患HCC的风险（OR=0．422，95％CI：0．179-0．994）。结论IL-6（rs1800796）、mTOR（rs7211818，rs9674559，rs11653499）多态性与HCC易感性无关；女性携带STAT3（rs744166，rs3816769，rs6503695）CC基因型及EGFR（rs11543848）（AG＋GG）的个体患HCC的风险降低，但还需更大样本验证。Objective To elucidate the association of genetic polymorphisms of key molecules in JAK/STAT signaling pathway with susceptibility of hepatocellular carcinoma （HCC）. Methods A total of 367 HCC patients and 367 healthy controls were recruited in this sex- and age-matched case-control study. Genetic polymorphisms of IL-6 （rs1800796, -572C〉G） , STAT3 （rs744166, ＋ 26312T〉C; rs3816769, ＋ 42240T〉C; rs6503695, ＋ 40980T〉C） , EGFR （rs11543848, ＋ 142530A〉G）, and mTOR （rs7211818, ＋ 170278A〉G; rs9674559, ＋ 196983A〉 G; rs11653499, ＋65678G〉A） were genotyped using a mass spectrometry method. Odds ratio （OR） and 95% confidence interval （CI） were calculated. Results Genotype frequency of the 8 polymorphisms of IL-6, STAT3, EGFR, and mTOR were not significantly different between the patients with HCC and the controls. When stratified by sex, the female subjects who carried STAT3 ＋ 26312CC, ＋ 42240CC, or ＋ 40980CC had a decreased risk of HCC when compared to those who carried TT allele （OR=0.192, 95% CI： 0.047-0.784; OR=0.180, 95% CI： 0.045-0.725 ; 0R=0.198, 95% CI： 0.049-0.806, respectively）. When compared with AA genotype on the site of EGFR ＋ 142530, the （AG ＋ GG） genotype reduced the risk of HCC in women （OR= 0.422,95%CI： 0.179-0.994）. Conclusion The polymorphisms of IL-6 （rsl800796） and mTOR （rs7211818, rs9674559, and rs11653499） were not associated with the HCC susceptibility. Those carrying CC allele in three loci （rs744166, rs3816769, and rs6503695） of STAT3 and （AG ＋GG） in rs11543848 of EGFR had a decreased risk of HCC in women. However, these results need to be validated using larger sample size.

关 键 词：肝细胞癌 JAK/STAT信号通路 单核苷酸多态性 

分 类 号：R735.7[医药卫生—肿瘤]