Hum Mol Genet:科学家证实烟草可增加患癌基因活性

2012-12-26 Hum Mol Genet. 中国科学报 赵熙熙

香烟留给你的绝对不止衣服和指甲上的呛人气味。一项新的研究找到了有力证据,表明烟草的使用能够在化学上改变和影响那些已知可以增加罹患癌症风险的基因的活性。这项研究或许能够为研究人员提供新的工具,用以评估吸烟人群的癌症风险。 脱氧核糖核酸(DNA)并不是命中注定的。能够影响基因功能的化合物可以与我们的遗传物质结合,从而开启或关闭某些基因。这些所谓的后天修饰能够影响各种各样的特征,例如肥胖和性取向。

香烟留给你的绝对不止衣服和指甲上的呛人气味。一项新的研究找到了有力证据,表明烟草的使用能够在化学上改变和影响那些已知可以增加罹患癌症风险的基因的活性。这项研究或许能够为研究人员提供新的工具,用以评估吸烟人群的癌症风险。

脱氧核糖核酸(DNA)并不是命中注定的。能够影响基因功能的化合物可以与我们的遗传物质结合,从而开启或关闭某些基因。这些所谓的后天修饰能够影响各种各样的特征,例如肥胖和性取向。科学家甚至已经确定了吸烟人群基因的特定表观遗传模式。然而,由于没有发现修改后的基因与癌症任何直接联系,因此科学家并不清楚这些化学变化是否增加了罹患癌症的风险。

在发表于《人类分子遗传学》杂志上的这项最新研究中,研究人员分析了来自374名个体的血细胞后生特征,这些人都参与了一项欧洲癌症与营养前瞻性调查(EPIC)。正如人们所知道的那样,EPIC是一项目的在于搞清饮食、生活习惯和环境因素与癌症及其他慢性疾病发病率之间联系的大型研究。其中有一半受试者在第一次加入这项研究的5到7年后患上了结肠癌或乳腺癌,而另一半受试者则依然保持健康。

由英国伦敦帝国学院的人类遗传学家James Flanagan率领的这一研究团队,在那些作为“烟民”的研究受试者中发现了一种独特的“后生足迹”。与那些从未吸烟的人相比,这些人在其DNA的20个不同区域中具有更少的被称为甲基组的化学标记,后者是后生变化的一种常见类型。当研究人员将这项分析延伸到暴露在烟草烟雾下的一组单独病人和小鼠后,他们将后天修饰的范围缩小到之前被认为与癌症有微弱联系的4个基因的几个位点上。Flanagan 指出,所有这些变化都会增加这几种基因的活性。他说,尚不清楚为什么增加这些基因的活性能够导致癌症,但未曾患癌症的人通常不携带这些修饰。

美国爱荷华大学的行为遗传学家Robert Philibert指出,这项研究第一次在一种癌症基因的后天修饰与罹患这种疾病的风险之间建立了一种密切的联系。海德尔堡德国癌症研究中心的流行病学家Lutz Breitling强调:“据我所知,之前还没有一项全基因组的表观遗传学研究进行过这样的尝试——从最初的发现到重复实验证据。”

这项研究可能为评估吸烟人群的癌症风险开辟了一条新的道路。Flanagan表示:“之前有关吸烟的研究经常会要求人们填写问卷表……这里存在着明显的缺点和误差。”他说,新的研究使医生们只需简单对人们的DNA进行后生分析便将量化一个人的患癌风险成为了可能。


Background
A single CpG site within F2RL3 was recently found to be hypomethylated in peripheral blood genomic DNA from smokers compared to former and non-smokers.
Method
We performed two epigenome-wide association studies (EWAS) nested in a prospective healthy cohort using the Illumina 450K Methylation Beadchip. The two populations consisted of matched pairs of healthy individuals (n=374), of which half went on to develop breast or colon cancer. The association was analysed between methylation and smoking status, as well as cancer risk.
Results
In addition to the same locus in F2RL3, we report several loci that are hypomethylated in smokers compared to former and non-smokers, including an intragenic region of the aryl hydrocarbon receptor repressor gene (AHRR; cg05575921, p=2.31x10-15; effect size = 14%-17%), an intergenic CpG island on 2q37.1 (cg21566642, p=3.73x10-13; effect size = 12%), and a further intergenic region at 6p21.33 (cg06126421, p=4.96x10-11, effect size = 7%-8%). Bisulphite pyrosequencing validated six loci in a further independent population of healthy individuals (n=180). Methylation levels in AHRR were also significantly decreased (p<0.001) and expression increased (p=0.0047) in the lung tissue of current smokers compared to non-smokers. This was further validated in a mouse model of smoke exposure. We observed an association with breast cancer risk for the 2q37.1 locus (p=0.003, adjusted for smoking status), but not for the other loci associated with smoking.
Conclusion
These data show that smoking has a direct effect on the epigenome in lung tissue, which is also detectable in peripheral blood DNA and may contribute to cancer risk.
Acknowledgements
The authors wish it to be known that the first two authors should be regarded as joint First Authors. We acknowledge funding from Cancer Research UK, Breast Cancer Campaign, Medical Research Council UK, HuGeF Foundation (Italy), Imperial Biomedical Research Centre and the NIHR Respiratory Disease Biomedical Research Unit.

    

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    2013-10-18 cy0324
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    2013-07-31 canlab
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  4. [GetPortalCommentsPageByObjectIdResponse(id=2048491, encodeId=1ec62048491cf, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, 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 Oct 18 05:00:00 CST 2013, time=2013-10-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1733618, encodeId=1c871e33618ce, content=<a href='/topic/show?id=d4f412668a4' target=_blank style='color:#2F92EE;'>#NET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, 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=Wed Jul 31 14:00:00 CST 2013, time=2013-07-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1685878, encodeId=a6f016858e8f9, content=<a href='/topic/show?id=66f3e93862' target=_blank style='color:#2F92EE;'>#Genet#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, 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=Thu Jun 06 00:00:00 CST 2013, time=2013-06-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2066522, encodeId=12ae20665227c, content=<a href='/topic/show?id=425e41e8523' target=_blank style='color:#2F92EE;'>#基因活性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41785, encryptionId=425e41e8523, topicName=基因活性)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/1103841572/7F67E3BE360D6DD1D0A62E3E71E23CB6/100, createdBy=9d8a2500148, createdName=ms8888626721583891, createdTime=Mon May 20 12:00:00 CST 2013, time=2013-05-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1310162, encodeId=f3bc13101626e, content=<a href='/topic/show?id=53036e11185' target=_blank style='color:#2F92EE;'>#烟草#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67111, encryptionId=53036e11185, topicName=烟草)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6a8d381, createdName=mnda, createdTime=Fri Dec 28 09:00:00 CST 2012, time=2012-12-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1373828, encodeId=618c13e3828a4, content=<a href='/topic/show?id=3644e1286f1' target=_blank style='color:#2F92EE;'>#癌基因#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71286, encryptionId=3644e1286f1, topicName=癌基因)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ee7b365, createdName=zhucaizhong7766, createdTime=Fri Dec 28 09:00:00 CST 2012, time=2012-12-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1601313, encodeId=9933160131314, content=<a href='/topic/show?id=5baa5299111' target=_blank style='color:#2F92EE;'>#患癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=52991, encryptionId=5baa5299111, topicName=患癌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=888f18872716, createdName=lq0307, createdTime=Fri Dec 28 09:00:00 CST 2012, time=2012-12-28, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=2048491, encodeId=1ec62048491cf, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, 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 Oct 18 05:00:00 CST 2013, time=2013-10-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1733618, encodeId=1c871e33618ce, content=<a href='/topic/show?id=d4f412668a4' target=_blank style='color:#2F92EE;'>#NET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, 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=Wed Jul 31 14:00:00 CST 2013, time=2013-07-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1685878, encodeId=a6f016858e8f9, content=<a href='/topic/show?id=66f3e93862' target=_blank style='color:#2F92EE;'>#Genet#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, 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=Thu Jun 06 00:00:00 CST 2013, time=2013-06-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2066522, encodeId=12ae20665227c, content=<a href='/topic/show?id=425e41e8523' target=_blank style='color:#2F92EE;'>#基因活性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41785, encryptionId=425e41e8523, topicName=基因活性)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/1103841572/7F67E3BE360D6DD1D0A62E3E71E23CB6/100, createdBy=9d8a2500148, createdName=ms8888626721583891, createdTime=Mon May 20 12:00:00 CST 2013, time=2013-05-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1310162, encodeId=f3bc13101626e, content=<a href='/topic/show?id=53036e11185' target=_blank style='color:#2F92EE;'>#烟草#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67111, encryptionId=53036e11185, topicName=烟草)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6a8d381, createdName=mnda, createdTime=Fri Dec 28 09:00:00 CST 2012, time=2012-12-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1373828, encodeId=618c13e3828a4, content=<a href='/topic/show?id=3644e1286f1' target=_blank style='color:#2F92EE;'>#癌基因#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71286, encryptionId=3644e1286f1, topicName=癌基因)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ee7b365, createdName=zhucaizhong7766, createdTime=Fri Dec 28 09:00:00 CST 2012, time=2012-12-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1601313, encodeId=9933160131314, content=<a href='/topic/show?id=5baa5299111' target=_blank style='color:#2F92EE;'>#患癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=52991, encryptionId=5baa5299111, topicName=患癌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=888f18872716, createdName=lq0307, createdTime=Fri Dec 28 09:00:00 CST 2012, time=2012-12-28, status=1, ipAttribution=)]
    2012-12-28 mnda
  6. [GetPortalCommentsPageByObjectIdResponse(id=2048491, encodeId=1ec62048491cf, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, 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 Oct 18 05:00:00 CST 2013, time=2013-10-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1733618, encodeId=1c871e33618ce, content=<a href='/topic/show?id=d4f412668a4' target=_blank style='color:#2F92EE;'>#NET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, 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=Wed Jul 31 14:00:00 CST 2013, time=2013-07-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1685878, encodeId=a6f016858e8f9, content=<a href='/topic/show?id=66f3e93862' target=_blank style='color:#2F92EE;'>#Genet#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, 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=Thu Jun 06 00:00:00 CST 2013, time=2013-06-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2066522, encodeId=12ae20665227c, content=<a href='/topic/show?id=425e41e8523' target=_blank style='color:#2F92EE;'>#基因活性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41785, encryptionId=425e41e8523, topicName=基因活性)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/1103841572/7F67E3BE360D6DD1D0A62E3E71E23CB6/100, createdBy=9d8a2500148, createdName=ms8888626721583891, createdTime=Mon May 20 12:00:00 CST 2013, time=2013-05-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1310162, encodeId=f3bc13101626e, content=<a href='/topic/show?id=53036e11185' target=_blank style='color:#2F92EE;'>#烟草#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67111, encryptionId=53036e11185, topicName=烟草)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6a8d381, createdName=mnda, createdTime=Fri Dec 28 09:00:00 CST 2012, time=2012-12-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1373828, encodeId=618c13e3828a4, content=<a href='/topic/show?id=3644e1286f1' target=_blank style='color:#2F92EE;'>#癌基因#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71286, encryptionId=3644e1286f1, topicName=癌基因)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ee7b365, createdName=zhucaizhong7766, createdTime=Fri Dec 28 09:00:00 CST 2012, time=2012-12-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1601313, encodeId=9933160131314, content=<a href='/topic/show?id=5baa5299111' target=_blank style='color:#2F92EE;'>#患癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=52991, encryptionId=5baa5299111, topicName=患癌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=888f18872716, createdName=lq0307, createdTime=Fri Dec 28 09:00:00 CST 2012, time=2012-12-28, status=1, ipAttribution=)]
  7. [GetPortalCommentsPageByObjectIdResponse(id=2048491, encodeId=1ec62048491cf, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, 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 Oct 18 05:00:00 CST 2013, time=2013-10-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1733618, encodeId=1c871e33618ce, content=<a href='/topic/show?id=d4f412668a4' target=_blank style='color:#2F92EE;'>#NET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, 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=Wed Jul 31 14:00:00 CST 2013, time=2013-07-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1685878, encodeId=a6f016858e8f9, content=<a href='/topic/show?id=66f3e93862' target=_blank style='color:#2F92EE;'>#Genet#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, 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=Thu Jun 06 00:00:00 CST 2013, time=2013-06-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2066522, encodeId=12ae20665227c, content=<a href='/topic/show?id=425e41e8523' target=_blank style='color:#2F92EE;'>#基因活性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41785, encryptionId=425e41e8523, topicName=基因活性)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/1103841572/7F67E3BE360D6DD1D0A62E3E71E23CB6/100, createdBy=9d8a2500148, createdName=ms8888626721583891, createdTime=Mon May 20 12:00:00 CST 2013, time=2013-05-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1310162, encodeId=f3bc13101626e, content=<a href='/topic/show?id=53036e11185' target=_blank style='color:#2F92EE;'>#烟草#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67111, encryptionId=53036e11185, topicName=烟草)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6a8d381, createdName=mnda, createdTime=Fri Dec 28 09:00:00 CST 2012, time=2012-12-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1373828, encodeId=618c13e3828a4, content=<a href='/topic/show?id=3644e1286f1' target=_blank style='color:#2F92EE;'>#癌基因#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71286, encryptionId=3644e1286f1, topicName=癌基因)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ee7b365, createdName=zhucaizhong7766, createdTime=Fri Dec 28 09:00:00 CST 2012, time=2012-12-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1601313, encodeId=9933160131314, content=<a href='/topic/show?id=5baa5299111' target=_blank style='color:#2F92EE;'>#患癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=52991, encryptionId=5baa5299111, topicName=患癌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=888f18872716, createdName=lq0307, createdTime=Fri Dec 28 09:00:00 CST 2012, time=2012-12-28, status=1, ipAttribution=)]
    2012-12-28 lq0307