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

谢佳新; 殷建华; 张琪; 蒲蕊; 张玉伟; 鹿文英; 曹广文

Abstract

谢佳新,殷建华,张琪,蒲蕊,张玉伟,鹿文英,曹广文.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[J].Chinese journal of Epidemiology,2012,33(2):215-219

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

Received:September 06, 2011

DOI：

KeyWord: 肝细胞癌 JAK/STAT信号通路单核苷酸多态性

English Key Word: Hepatocellular carcinoma JAK/STAT signaling pathway Single nucleotide polymorphism

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

Author Name	Affiliation	E-mail
XIE Jia-xin	Department of Epidemiology f Second Military Medical University, Shanghai 200433, China
YIN Jian-hua	Department of Epidemiology f Second Military Medical University, Shanghai 200433, China
ZHANG Qi	Department of Epidemiology f Second Military Medical University, Shanghai 200433, China
PU Rui	Department of Epidemiology f Second Military Medical University, Shanghai 200433, China
ZHANG Yu-wei	Department of Epidemiology f Second Military Medical University, Shanghai 200433, China
LU Wen-ying	Department of Epidemiology f Second Military Medical University, Shanghai 200433, China
CA0 Guang-wen	Department of Epidemiology f Second Military Medical University, Shanghai 200433, China	gcao@smmu.edu.cn

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Abstract:

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11^-6(>81800796, -57200)、81/\丁3(^744166, +263121'>C;rs3816769, +42240T>C；rs6503695, +40980T>C)、EGFR(rsll543848, +142530A>G)、mTOR(rs7211818, +170278A>G;rs9674559, +196983A>G;rsll653499, +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(Oi?)和95%可信区间(C/)。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)o按性别分层后, 在女性中, 与TT基因型相比, 携带STAT3+26312CC、+42240CC、+40980CC基因型个体患HCC的危险性降低(0fi=0.192, 95%C7：0.047~0.784;Off=0.180, 95%C/:0.045~0.725;OR=0.198, 95%C/: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(0/?=0.422, 95%C/: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。

English Abstract:

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(rsll543848, + 142530A>G), and mTOR(rs7211818, + 170278A>G; rs9674559, + 196983A>G； rsl 1653499, +65678G>A) were genotyped using a mass spectrometry method. Odds ratio(OR) and 95% confidence interval(Cl) 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(0/?=0.192, 95%Cl:0.047-0.784； OR=0.180, 95%Cl:0.045-0.725；OR=0.198, 95% Cl: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 rsl 1653499) were not associated with the HCC susceptibility. Those carrying CC allele in three loci(rs744166, rs3816769, and rs6503695) of STAT3 and(AG + GG) in rsl 1543848 of EGFR had a decreased risk of HCC in women. However, these results need to be validated using larger sample size.

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