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Nat Genet:携带BRCA2突变的吸烟者更易患上肺癌

2014-06-10 佚名 不详

最近的一项新研究证实,BRCA2和CHEK2基因变异,特别是突变型BRCA2,可以大大增加个人患肺癌的风险。如果吸烟者携带BRCA2变异,其患肺癌的风险可能翻倍。 由伦敦癌症研究所、法国国际癌症研究机构、美国国家癌症研究所和美国达特茅斯学院等研究结构组成的国际合作小组,利用来自1000个肺癌遗传学研究基因组项目的综合结果,完成了这一研究,相关结果发表在2014年6月1日的《自然遗传学》(Natu

最近的一项新研究证实,BRCA2和CHEK2基因变异,特别是突变型BRCA2,可以大大增加个人患肺癌的风险。如果吸烟者携带BRCA2变异,其患肺癌的风险可能翻倍。

由伦敦癌症研究所、法国国际癌症研究机构、美国国家癌症研究所和美国达特茅斯学院等研究结构组成的国际合作小组,利用来自1000个肺癌遗传学研究基因组项目的综合结果,完成了这一研究,相关结果发表在2014年6月1日的《自然遗传学》(Nature Genetics)。

研究扫描了1.1万多欧洲血统人口的基因组,寻找非小细胞癌(肺癌的常见形式)相关的常见变异。分析表明,BRCA2和CHEK2基因变异,可以大大增加肺癌的个人发展风险。如果吸烟者携带BRCA2变异,其罹患肺癌的风险可能翻倍。此外,在这些欧洲血统人口中,TP63基因(以前认为只与在亚洲人肺癌风险相关)与腺癌(一种非小细胞肺癌)的风险有关。

本研究利用来自于德克萨斯大学M.D.安德森癌症中心、英国癌症研究院、美国国家癌症研究所和国际癌症研究机构的四项全基因组关联(GWA)研究。科学家们使用基因填补(imputation)计算——一种基于观察对象已有基因型,对未进行基因分型的位点之等位基因进行预测的方法。

本文资深作者、达特茅斯基因组医学中心主任Chris Amos博士称:“这种计算方法,使我们通过全基因组关联研究,发现了迄今最强的癌症关联,并确定了一部分人,他们特别容易受到吸烟相关的伤害。”

BRCA2基因编码一个非常大的蛋白质,主要功能是协调许多不同DNA修复相关基因的活动。由于环境毒素(如包含在烟草烟雾中的毒素),细胞会积聚DNA损伤。BRCA2突变可能会影响细胞响应DNA损伤的能力,增加细胞变成癌症的机会。

以前的研究并没有发现BRCA2和肺癌之间的关系。在这项研究中,所有四个GWA数据集分析均表明,BRCA2基因(rs11571833)和非小细胞肺癌(特别是鳞状细胞癌)之间存在显著的关联。此外,结果证实了以前的研究,将CHEK2 (rs17879961)与鳞状细胞癌联系在一起。在欧洲血统人口中发现的TP63 (rs13314271)变异,有力证明了其与腺癌之间的关联。

该研究负责人、英国癌症研究所分子和群体遗传学教授Richard Houlston称:“我们的研究表明,在吸烟的情况下,BRCA2和CHEK2两个基因的突变,对肺癌风险具有很大的影响。特别是突变型BRCA2,可能增加1.8倍的风险。一般吸烟者患肺癌的可能性接近于15%,远高于非吸烟者。我们的研究结果表明,一些携带BRCA2突变的吸烟者,具有患上肺癌的巨大风险(25%)。每年,肺癌夺去全世界超过100万人的生命,是迄今为止最大的癌症杀手。我们知道,对于降低死亡率而言,我们唯一可以做的就是,说服人们不要吸烟,我们的新研究清楚的表明,对于具有潜在遗传风险的人来说,戒烟尤为重要。”

这项研究结果,可能会影响肺癌患者的筛选和治疗。携带基因突变的吸烟者,可能是低剂量CT扫描筛查肺癌的候选人。由于携带BRCA1或BRCA2胚系突变的人,对一种特定的化疗方法(称为PARP抑制)有反应,因此,比其他肺癌病例相比,携带这个BRCA2突变的肺癌患者,可能同样会积极地响应PARP抑制疗法。

原始出处

Wang Y1, McKay JD2, Rafnar T3, Wang Z4, Timofeeva MN5, Broderick P6, Zong X7, Laplana M8, Wei Y9, Han Y10, Lloyd A6, Delahaye-Sourdeix M5, Chubb D6, Gaborieau V5, Wheeler W11, Chatterjee N4, Thorleifsson G3, Sulem P3, Liu G12, Kaaks R13, Henrion M6, Kinnersley B6, Vallée M5, LeCalvez-Kelm F5, Stevens VL14, Gapstur SM14, Chen WV15, Zaridze D16, Szeszenia-Dabrowska N17, Lissowska J18, Rudnai P19, Fabianova E20, Mates D21, Bencko V22, Foretova.Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer.Nat Genet. 2014 Jun 1

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    2015-01-07 liye789132251
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    2014-10-26 canlab
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    2014-06-18 智智灵药
  4. [GetPortalCommentsPageByObjectIdResponse(id=1880105, encodeId=e88e1880105db, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Wed Jan 07 06:25:00 CST 2015, time=2015-01-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1733692, encodeId=4f9d1e336923f, content=<a href='/topic/show?id=d4f412668a4' target=_blank style='color:#2F92EE;'>#NET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, 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=Sun Oct 26 07:25:00 CST 2014, time=2014-10-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2048594, encodeId=d60420485948f, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=智智灵药, createdTime=Wed Jun 18 03:25:00 CST 2014, time=2014-06-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1715648, encodeId=90d81e15648af, content=<a href='/topic/show?id=e5893694bc' target=_blank style='color:#2F92EE;'>#BRCA2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3694, encryptionId=e5893694bc, topicName=BRCA2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=bd2531999527, createdName=yige2014, createdTime=Mon Dec 08 05:25:00 CST 2014, time=2014-12-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1685947, encodeId=f99b168594ee4, content=<a href='/topic/show?id=66f3e93862' target=_blank style='color:#2F92EE;'>#Genet#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=126, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7938, encryptionId=66f3e93862, topicName=Genet)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=智智灵药, createdTime=Wed Aug 27 05:25:00 CST 2014, time=2014-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1593984, encodeId=d9f7159398450, content=<a href='/topic/show?id=63cc368459' target=_blank style='color:#2F92EE;'>#BRCA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3684, encryptionId=63cc368459, topicName=BRCA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=918e18200218, createdName=cmj14wellington, createdTime=Thu Jun 12 00:25:00 CST 2014, time=2014-06-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1602835, encodeId=7af216028351d, content=<a href='/topic/show?id=e0b5393680' target=_blank style='color:#2F92EE;'>#CA2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3936, encryptionId=e0b5393680, topicName=CA2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=03ab18968787, createdName=TZF0810, createdTime=Thu Jun 12 00:25:00 CST 2014, time=2014-06-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1605083, encodeId=f09b1605083cf, content=<a href='/topic/show?id=5cba39435fd' target=_blank style='color:#2F92EE;'>#吸烟者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=39435, encryptionId=5cba39435fd, topicName=吸烟者)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cc8619318136, createdName=124984e7m89暂无昵称, createdTime=Thu Jun 12 00:25:00 CST 2014, time=2014-06-12, status=1, ipAttribution=)]
    2014-12-08 yige2014
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    2014-06-12 TZF0810
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