Xie Jia-xin, Yin Jian-hua, Zhang Qi, Pu Rui, Zhang Yu-wei, Lu Wen-ying, Cao Guang-wen
Department of Epidemiology, Second Military Medical University, Shanghai, China.
Zhonghua Liu Xing Bing Xue Za Zhi. 2012 Feb;33(2):215-9.
To elucidate the association of genetic polymorphisms of key molecules in JAK/STAT signaling pathway with susceptibility of hepatocellular carcinoma (HCC).
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.
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; OR = 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).
The polymorphisms of IL-6 (rs1800796) 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.
阐明JAK/STAT信号通路中关键分子的基因多态性与肝细胞癌（HCC）易感性的关联。
在这项性别和年龄匹配的病例对照研究中，共招募了367例HCC患者和367名健康对照。采用质谱法对白细胞介素-6（IL-6，rs1800796，-572C＞G）、信号转导和转录激活因子3（STAT3，rs744166，+26312T＞C；rs3816769，+42240T＞C；rs6503695，+40980T＞C）、表皮生长因子受体（EGFR，rs11543848，+142530A＞G）和雷帕霉素靶蛋白（mTOR，rs7211818，+170278A＞G；rs9674559，+196983A＞G；rs11653499，+65678G＞A）的基因多态性进行基因分型。计算比值比（OR）和95%置信区间（CI）。
HCC患者与对照组之间，IL-6、STAT3、EGFR和mTOR的8种多态性的基因型频率无显著差异。按性别分层时，携带STAT3 +26312CC、+42240CC或+40980CC的女性受试者患HCC的风险低于携带TT等位基因的女性（OR分别为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EGFR +142530位点的AA基因型相比，（AG + GG）基因型降低了女性患HCC的风险（OR = 0.422，95%CI：0.179 - 0.994）。
IL-6（rs1800796）和mTOR（rs7211818、rs9674559和rs11653499）的多态性与HCC易感性无关。携带STAT3三个位点（rs744166、rs3816769和rs6503695）的CC等位基因以及EGFR的rs11543848中的（AG + GG）基因型的女性患HCC的风险降低。然而，这些结果需要用更大的样本量进行验证。
