STAT3和STAT4基因单核苷酸多态性与肝细胞癌的相关性
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摘要
目的探讨信号传导和转录激活因子3(STAT3)基因rs2293152位点和信号传导和转录激活因子4(STAT4)基因rs7574865位点单核苷酸多态性(SNPs)与肝细胞癌(HCC)遗传易感性的关联及与环境因素的交互作用。方法采用病例对照研究方法,选取HCC患者256例作为观察组,同期健康体检者256例作为对照组,检测两组rs2293152、rs7574865位点SNPs。采用二分类Logistic回归模型分析rs2293152、rs7574865位点SNPs与HCC遗传易感性的关系,并探究rs2293152、rs7574865位点SNPs与环境因素的交互作用对HCC发病影响。结果两组间rs2293152、rs7574865位点基因型分布差异均无统计学意义(P> 0.05)。rs2293152位点G等位基因和rs7574865位点G等位基因均可显著增加HCC发病风险(P <0.05)。在饮酒与乙型肝炎病毒(HBV)感染人群中,rs2293152位点GG基因型相比GC+CC基因型,rs7574865位点GG基因型相比GT+TT基因型,HCC发病风险均显著升高(P <0.05)。rs2293152、rs7574865位点SNPs与饮酒、HBV感染均存在正交互作用。结论STAT3基因rs2293152位点和STAT4基因rs7574865位点SNPs与HCC遗传易感性明显相关,并与饮酒、HBV感染存在正交互作用,可增加HCC发病风险。
Objective To investigate the associations of single-nucleotide polymorphisms(SNPs) ofSTAT3 and STAT4 with the hereditary susceptibility of hepatocellular carcinoma(HCC),and their interactionswith environmental factors. Methods This study was a case-control study. 256 hepatocellular carcinoma(HCC)patients were enrolled as the study group and 256 subjects undergoing physical examination at the same period wereenrolled as the control group. The genotypes of locus rs229315 at STAT3 and rs7574865 at STAT4 were detected.Binary logistic regression analyses were used to explore the associations between SNPs of rs229315 and rs7574865 and the hereditary susceptibility of HCC,and their interactions with environmental factors. Results(1)No signif-icant difference was observed between the two groups in the distribution of STAT3 rs229315 or STAT4 rs7574865 genotypes(P > 0.05).(2)STAT3 rs229315 G alley and STAT4 rs7574865 G alley increased the risk of HCC(P < 0.05).(3)Stratified analysis found that in alcohol or hepatitis B virus(HBV)infected people,rs2293152 GG genotype compared to GC + CC genotype,and rs7574865 GG genotype compared to GT + TT genotype,therisk of HCC elevated(P < 0.05).(4)Gene-environment interaction assay indicated the SNP of STAT3 rs229315 was positively interacted with alcohol and HBV infection,and so was that of STAT4 rs7574865. Conclusions TheSNPs of STAT3 rs229315 and STAT4 rs7574865 are closely related with the hereditary susceptibility of HCC,andpositively interacts with alcohol,and HBV infection,which could increase the risk of HCC.
Objective To investigate the associations of single-nucleotide polymorphisms(SNPs) ofSTAT3 and STAT4 with the hereditary susceptibility of hepatocellular carcinoma(HCC),and their interactionswith environmental factors. Methods This study was a case-control study. 256 hepatocellular carcinoma(HCC)patients were enrolled as the study group and 256 subjects undergoing physical examination at the same period wereenrolled as the control group. The genotypes of locus rs229315 at STAT3 and rs7574865 at STAT4 were detected.Binary logistic regression analyses were used to explore the associations between SNPs of rs229315 and rs7574865 and the hereditary susceptibility of HCC,and their interactions with environmental factors. Results(1)No signif-icant difference was observed between the two groups in the distribution of STAT3 rs229315 or STAT4 rs7574865 genotypes(P > 0.05).(2)STAT3 rs229315 G alley and STAT4 rs7574865 G alley increased the risk of HCC(P < 0.05).(3)Stratified analysis found that in alcohol or hepatitis B virus(HBV)infected people,rs2293152 GG genotype compared to GC + CC genotype,and rs7574865 GG genotype compared to GT + TT genotype,therisk of HCC elevated(P < 0.05).(4)Gene-environment interaction assay indicated the SNP of STAT3 rs229315 was positively interacted with alcohol and HBV infection,and so was that of STAT4 rs7574865. Conclusions TheSNPs of STAT3 rs229315 and STAT4 rs7574865 are closely related with the hereditary susceptibility of HCC,andpositively interacts with alcohol,and HBV infection,which could increase the risk of HCC.
引文
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[7]ZHANG L,XU K,LIU C,et al.Meta-analysis reveals an association between signal transducer and activator of transcription-4 polymorphism and hepatocellular carcinoma risk[J].Hepatol Res,2017,47(4):303-311.
[8]XIE J,ZHANG Y,ZHANG Q,et al.Interaction of signal transducer and activator of transcription 3 polymorphisms with hepatitis B virus mutations in hepatocellular carcinoma[J].Hepatology,2013,57(6):2369-2377.
[9]姚伦凯,柳广南,黄斯明,等.肺腺癌组织中HDAC2、IL-8、TNF-α的表达及其与吸烟的关系[J].中华医学杂志,2016,96(18):1410-1413.
[10]朴金梅,刘梦,李成成,等.STAT4 rs7574865GG基因型与GT+TT基因型肝癌患者相关危险因素对比分析[J].中华肿瘤防治杂志,2017,24(2):84-86.
[11]CHANTHRA N,PAYUNGPORN S,CHUAYPEN N,et al.Single nucleotide polymorphisms in STAT3 and STAT4 and risk of hepatocellular carcinoma in thai patients with chronic hepatitis B[J].Asian Pac J Cancer Prev,2015,16(18):8405-8410.
[12]TRAD D,BIBANI N,SABBAH M,et al.Known,new and emerging risk factors of hepatocellular carcinoma(review)[J].Presse Med,2017,46(11):1000-1007.
[13]NAHON P,NAULT J.Constitutional and functional genetics of human alcohol-related hepatocellular carcinoma[J].Liver Int,2017,37(11):1591-1601.
[14]MING W,DONG X,QIN N.Virus-induced hepatocellular carcinoma with special emphasis on HBV[J].Hepatol Int,2017,11(2):1-10.
[15]GAO X,YANG HI,JEONG D,et al.Antiviral therapy reduces hepatocellular carcinoma risk in HBV cirrhosis patients with lower viral load[J].Gastroenterology,2017,152(5):S1052-S1053.
[16]许侨东,颜永聪,黄拼搏,等.乙型肝炎病毒X蛋白在肝细胞癌中的病理作用及相关分子机制[J].实用医学杂志,2016,32(20):3448-3450.2018-04-23
[2]ZHU Z X,HUANG J W,LIAO M H,et al.Treatment strategy for hepatocellular carcinoma in China:radiofrequency ablation versus liver resection[J].Jpn J Clin Oncol,2016,46(12):1075-1080.
[3]SUBRAMANIAM A,SHANMUGAM M K,PERUMAL E,et al.Potential role of signal transducer and activator of transcription(STAT)3 signaling pathway in inflammation,survival,3602proliferation and invasion of hepatocellular carcinoma[J].Biochim Biophys Acta,2013,1835(1):46-60.
[4]廖明媚,王成志,杨满意,等.JAK2-STAT3信号通路在肝细胞癌中的研究进展[J].中国普通外科杂志,2017,26(1):102-108.
[5]ZHAO X,JIANG K,LIANG B,et al.STAT4 gene polymorphism and risk of chronic hepatitis B-induced hepatocellular carcinoma[J].Cell Biochem Biophys,2015,71(1):353-357.
[6]JIANG DK,SUN J,CAO G,et al.Genetic variants in STAT4and HLA-DQ genes confer risk of hepatitis B virus-related hepatocellular carcinoma[J].Nat Genet,2013,45(1):72-75.
[7]ZHANG L,XU K,LIU C,et al.Meta-analysis reveals an association between signal transducer and activator of transcription-4 polymorphism and hepatocellular carcinoma risk[J].Hepatol Res,2017,47(4):303-311.
[8]XIE J,ZHANG Y,ZHANG Q,et al.Interaction of signal transducer and activator of transcription 3 polymorphisms with hepatitis B virus mutations in hepatocellular carcinoma[J].Hepatology,2013,57(6):2369-2377.
[9]姚伦凯,柳广南,黄斯明,等.肺腺癌组织中HDAC2、IL-8、TNF-α的表达及其与吸烟的关系[J].中华医学杂志,2016,96(18):1410-1413.
[10]朴金梅,刘梦,李成成,等.STAT4 rs7574865GG基因型与GT+TT基因型肝癌患者相关危险因素对比分析[J].中华肿瘤防治杂志,2017,24(2):84-86.
[11]CHANTHRA N,PAYUNGPORN S,CHUAYPEN N,et al.Single nucleotide polymorphisms in STAT3 and STAT4 and risk of hepatocellular carcinoma in thai patients with chronic hepatitis B[J].Asian Pac J Cancer Prev,2015,16(18):8405-8410.
[12]TRAD D,BIBANI N,SABBAH M,et al.Known,new and emerging risk factors of hepatocellular carcinoma(review)[J].Presse Med,2017,46(11):1000-1007.
[13]NAHON P,NAULT J.Constitutional and functional genetics of human alcohol-related hepatocellular carcinoma[J].Liver Int,2017,37(11):1591-1601.
[14]MING W,DONG X,QIN N.Virus-induced hepatocellular carcinoma with special emphasis on HBV[J].Hepatol Int,2017,11(2):1-10.
[15]GAO X,YANG HI,JEONG D,et al.Antiviral therapy reduces hepatocellular carcinoma risk in HBV cirrhosis patients with lower viral load[J].Gastroenterology,2017,152(5):S1052-S1053.
[16]许侨东,颜永聪,黄拼搏,等.乙型肝炎病毒X蛋白在肝细胞癌中的病理作用及相关分子机制[J].实用医学杂志,2016,32(20):3448-3450.2018-04-23