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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 被引量:8

Association of genetic polymorphisms of key molecules in JAK/STAT signaling pathway with susceptibility of hepatocellular carcinoma
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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.
出处 《中华流行病学杂志》 CAS CSCD 北大核心 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)
关键词 肝细胞癌 JAK/STAT信号通路 单核苷酸多态性 Hepatocellular carcinoma JAK/STAT signaling pathway Single nucleotide polymorphism
作者简介 通信作者:曹广文,Email:gcao@smmu.edu.cn
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