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NAT GENET:STAT4和HLA-DQ基因可能是乙肝癌变关键基因

2012-12-19 MedSci NAT GENET

     肝癌是全世界致死率高居第三的恶性肿瘤,也是中国常见的一种恶性疾病。全球每年约有70万人死于肝癌,而我国卫生部统计数据显示,全国每年有35-40万的肝癌新发病例,占全世界肝癌病人总数的一半以上。病史调查表明,我国的肝癌病人中80%以上都有乙肝病史。我国目前总计有9300万乙肝病人,占全世界乙肝患者总数的三分之一以上。统计数据显示,并非所有乙肝病人都会发展成为肝癌患者,那么究竟是什么导致乙

肝癌  

  肝癌是全世界致死率高居第三的恶性肿瘤,也是中国常见的一种恶性疾病。全球每年约有70万人死于肝癌,而我国卫生部统计数据显示,全国每年有35-40万的肝癌新发病例,占全世界肝癌病人总数的一半以上。病史调查表明,我国的肝癌病人中80%以上都有乙肝病史。我国目前总计有9300万乙肝病人,占全世界乙肝患者总数的三分之一以上。统计数据显示,并非所有乙肝病人都会发展成为肝癌患者,那么究竟是什么导致乙肝癌变呢?如何防治乙肝,尤其是尽量防止乙肝患者发生癌变?科学家们一直希望找到肝癌易感基因,但却没有明确的结果。

  乙肝癌变的关键风险基因终于被科学家发现。12月17日凌晨,《自然·遗传学》杂志在线发表了由复旦大学遗传学研究所、遗传工程国家重点实验室余龙教授花费12年时间领衔完成的一项重大研究成果,确定人的STAT4和HLA-DQ基因是乙肝患者罹患肝癌的关键易感基因。这为科学家们预测并提前干预乙肝的癌变提供了可能性。

  基因是生命遗传的基本单位,由2.5万个基因、30亿个碱基对组成的人体基因组,蕴藏着生命的奥秘。复旦大学余龙课题组联系了国内外30个课题组,66位学者开展协作攻关,收集了国内7个地区的独立人群、总计11799例乙型肝炎患者的血细胞DNA样本。包括5480例有乙肝病变的肝癌病例和6319例有乙肝病史但无肝癌的对照者。运用全基因组关联分析技术,比对分析了两组人群的全基因组序列中近73万个单核苷酸多态位点的等位基因频率,最终在STAT4基因和HLA-DQ基因簇上发现了与乙肝癌变风险显著关联的易感基因位点。

  据介绍,STAT4基因位于人的2号染色体,可能在抗病毒、抗肿瘤和免疫应答中发挥重要的“预警”作用。这一基因可以调控人体内炎症的发展和肿瘤的生长。HLA-DQ基因簇位于人的6号染色体,包含HLA-DQA1、HLA-DQB1、HLA-DQA2、HLA-DQB2等基因。HLA-DQ基因簇编码的蛋白质的主要功能是参与免疫调节,如调节免疫细胞分化、约束免疫细胞间的相互作用,以及对免疫应答的遗传调控等,从而使免疫系统能够保持强大功能,维持人体的健康。而课题组发现,有乙肝病史但是没有肝癌病变的患者与有乙肝病史,但是有肝癌病变的患者,主要在这两个基因位点上有不同的表现形态。

  论文的第一作者、复旦大学遗传所的蒋德科博士说,两个易感基因位点的发现,为人类进一步研究如何降低肝癌发病风险、治疗乙肝和肝癌指出了新的方向。蒋德科博士告诉记者,利用这一研究成果,可以开发肝癌的基因预警试剂,筛查肝癌的易感人群,从而提前对易感人群进行相应的综合干预和预防措施,降低肝癌发病风险。现在科学家们对于包括前列腺癌、乳腺癌等各种癌症都在做相类似的工作,也都找到了一些易感基因,但是离真正的运用还有很长的距离。

  复旦大学遗传工程国家重点实验室肿瘤分子遗传学课题组,是2000年首批国家自然科学基金委“创新研究群体”之一。课题组组长、这一最新成果的通讯作者余龙教授介绍说,12年来,课题组选定了对国家有战略需求的重大科学问题,长期坚持以肝癌防治为目标,持续探讨肝癌发生发展的分子机制,终有今天的成果。据介绍,自2000年入选创新研究团队,复旦遗传工程国家重点实验室肿瘤分子遗传学课题组已在《肝病学》、《肠道疾病》、《临床癌症研究》等国际SCI杂志发表论文200余篇。

乙肝相关的拓展阅读:




To identify genetic susceptibility loci for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in the Chinese population, we carried out a genome-wide association study (GWAS) in 2,514 chronic HBV carriers (1,161 HCC cases and 1,353 controls) followed by a 2-stage validation among 6 independent populations of chronic HBV carriers (4,319 cases and 4,966 controls). The joint analyses showed that HCC risk was significantly associated with two independent loci: rs7574865 atSTAT4Pmeta = 2.48 × 10−10, odds ratio (OR) = 1.21; and rs9275319 at HLA-DQ, Pmeta = 2.72 × 10−17, OR = 1.49. The risk allele G at rs7574865 was significantly associated with lower mRNA levels of STAT4 in both the HCC tissues and nontumor tissues of 155 individuals with HBV-related HCC (Ptrend = 0.0008 and 0.0002, respectively). We also found significantly lower mRNA expression of STAT4 in HCC tumor tissues compared with paired adjacent nontumor tissues (P = 2.33 × 10−14).    

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    2013-09-02 liye789132251
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    2013-11-08 cy0324
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    2013-03-30 canlab
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    2013-01-21 zhu_jun9837
  7. [GetPortalCommentsPageByObjectIdResponse(id=1879397, encodeId=ee0b18e9397dc, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Mon Sep 02 23:00:00 CST 2013, time=2013-09-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1986844, encodeId=7cfc198684408, content=<a href='/topic/show?id=d92e301e1a2' target=_blank style='color:#2F92EE;'>#关键基因#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30171, encryptionId=d92e301e1a2, topicName=关键基因)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ec9955, createdName=windight, createdTime=Wed Jan 09 08:00:00 CST 2013, time=2013-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2048489, encodeId=534f204848998, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Fri Nov 08 05:00:00 CST 2013, time=2013-11-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1685876, encodeId=0f9d16858e6eb, content=<a href='/topic/show?id=66f3e93862' target=_blank style='color:#2F92EE;'>#Genet#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7938, encryptionId=66f3e93862, topicName=Genet)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d3e128296421, createdName=江川靖瑶, createdTime=Tue May 07 19:00:00 CST 2013, time=2013-05-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1733616, encodeId=4a4a1e33616a5, content=<a href='/topic/show?id=d4f412668a4' target=_blank style='color:#2F92EE;'>#NET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12668, encryptionId=d4f412668a4, topicName=NET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7ea033781210, createdName=canlab, createdTime=Sat Mar 30 09:00:00 CST 2013, time=2013-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1794303, encodeId=91601e94303c0, content=<a href='/topic/show?id=e36516e561a' target=_blank style='color:#2F92EE;'>#STAT4#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16756, encryptionId=e36516e561a, topicName=STAT4)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3609256, createdName=zhu_jun9837, createdTime=Mon Jan 21 19:00:00 CST 2013, time=2013-01-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1502021, encodeId=4aea150202129, content=<a href='/topic/show?id=14a6894190' target=_blank style='color:#2F92EE;'>#HLA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8941, encryptionId=14a6894190, topicName=HLA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e72c9501412, createdName=marongnuan, createdTime=Fri Dec 21 07:00:00 CST 2012, time=2012-12-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1557018, encodeId=8d98155e0184f, content=<a href='/topic/show?id=154be128170' target=_blank style='color:#2F92EE;'>#癌变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71281, encryptionId=154be128170, topicName=癌变)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cd7914850828, createdName=axin014, createdTime=Fri Dec 21 07:00:00 CST 2012, time=2012-12-21, status=1, ipAttribution=)]
    2012-12-21 marongnuan
  8. [GetPortalCommentsPageByObjectIdResponse(id=1879397, encodeId=ee0b18e9397dc, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Mon Sep 02 23:00:00 CST 2013, time=2013-09-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1986844, encodeId=7cfc198684408, content=<a href='/topic/show?id=d92e301e1a2' target=_blank style='color:#2F92EE;'>#关键基因#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30171, encryptionId=d92e301e1a2, topicName=关键基因)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ec9955, createdName=windight, createdTime=Wed Jan 09 08:00:00 CST 2013, time=2013-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2048489, encodeId=534f204848998, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Fri Nov 08 05:00:00 CST 2013, time=2013-11-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1685876, encodeId=0f9d16858e6eb, content=<a href='/topic/show?id=66f3e93862' target=_blank style='color:#2F92EE;'>#Genet#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7938, encryptionId=66f3e93862, topicName=Genet)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d3e128296421, createdName=江川靖瑶, createdTime=Tue May 07 19:00:00 CST 2013, time=2013-05-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1733616, encodeId=4a4a1e33616a5, content=<a href='/topic/show?id=d4f412668a4' target=_blank style='color:#2F92EE;'>#NET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12668, encryptionId=d4f412668a4, topicName=NET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7ea033781210, createdName=canlab, createdTime=Sat Mar 30 09:00:00 CST 2013, time=2013-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1794303, encodeId=91601e94303c0, content=<a href='/topic/show?id=e36516e561a' target=_blank style='color:#2F92EE;'>#STAT4#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16756, encryptionId=e36516e561a, topicName=STAT4)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3609256, createdName=zhu_jun9837, createdTime=Mon Jan 21 19:00:00 CST 2013, time=2013-01-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1502021, encodeId=4aea150202129, content=<a href='/topic/show?id=14a6894190' target=_blank style='color:#2F92EE;'>#HLA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8941, encryptionId=14a6894190, topicName=HLA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e72c9501412, createdName=marongnuan, createdTime=Fri Dec 21 07:00:00 CST 2012, time=2012-12-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1557018, encodeId=8d98155e0184f, content=<a href='/topic/show?id=154be128170' target=_blank style='color:#2F92EE;'>#癌变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71281, encryptionId=154be128170, topicName=癌变)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cd7914850828, createdName=axin014, createdTime=Fri Dec 21 07:00:00 CST 2012, time=2012-12-21, status=1, ipAttribution=)]
    2012-12-21 axin014
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