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Lancet Oncol:宫颈癌前病变和浸润性宫颈癌的易感遗传变异!

2021-04-19 Nebula MedSci原创

为什么有的人感染了HPV可以自愈,而有的人则会发展为宫颈癌?

大多数宫颈高危型人乳头状瘤病毒(HPV)感染是一过性的,只有一小部分HPV感染者会发展为宫颈癌。为什么有的人感染了HPV可以自愈,而有的人则会发展为宫颈癌?

家庭聚集性研究和遗传力评估表明,这可能是由遗传因素介导的。候选基因研究和既往的全基因组关联研究(GWAS)报告了HLA区域和宫颈癌之间的关联。

本研究采用全基因组方法,旨在比较浸润性宫颈癌和宫颈上皮内瘤变(CIN)3级患者与健康对照组的基因变异差异

研究人员利用英国生物库(UK Biobank)的数据对一组无血缘关系的欧洲人进行了GWAS检查,包括在2006年3月13日-2010年10月1日期间招募的273377位40-69岁的女性。采用加性单变量Logistic回归模型来分析与浸润性宫颈癌或CIN3相关的基因变异;在FinnGen中寻求候选关联的复制(FinnGen是一个包含128123人的大型独立数据集)。最后,研究人员进行了两个样本的孟德尔随机化方法,以探索危险因素在宫颈癌遗传风险中的作用。

总体上,本研究从GWAS中纳入了4769例CIN3和浸润性宫颈癌病例样本和145545例对照样本。

与CIN3级和浸润性宫颈癌相关的独立变异

在分析的9600464个单核苷酸多态性(SNP)位点中,有6个独立变异与CIN3级和浸润性宫颈癌相关。其中包括新基因位点rs10175462(PAX8;优势比[OR]0.87,95%CI 0.84-0.91;p=1.07×10-9)和rs27069(CLPTM1L;0.88,0.84-0.92;p=2.51×10-9),以及既往报道过的位点:rs9272050(HLA-DQA1;1.27,1.21-1.32;p=2.51×-28)、rs6938453 (MICA; 0.79, 0.75–0·83; p=1.97×10-17), rs55986091 (HLA-DQB1; 0.66, 0.60–0.72; p=6.42×10–22)和rs9266183(HLA-B;0.73,0.64-0.83;p=1.53×10-6)。

在1648例浸润性宫颈癌的独立数据集中捕获了三个SNP:Pax8(rs10175462;p=0.015)、CLPTM1L(rs27069;p=2.54×10-7)和HLA-DQA1(rs9272050;p=7.90×10-8)。

孟德尔随机化分析进一步支持吸烟(OR 2.46,95%CI 1.64-3.69)、首次怀孕年龄较大(0.80,0.68-0.95)和性伴侣数量较多(1.95,1.44-2.63)在宫颈癌风险中均具有一定贡献作用

综上,该研究结果为宫颈癌的遗传易感性提供了新的证据,特别是PAX8、CLPTM1L和HLA基因,提示凋亡和免疫功能途径受到干扰可能在宫颈癌的发生中具有重要作用

原始出处:

Bowden Sarah J,Bodinier Barbara,Kalliala Ilkka et al. Genetic variation in cervical preinvasive and invasive disease: a genome-wide association study. Lancet Oncol, 2021, 22: 548-557.

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    2021-12-19 howi
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    2021-07-09 minlingfeng
  4. 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topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160806/IMG57A5698BDB0244113.jpg, createdBy=32a91358059, createdName=jyzxjiangqin, createdTime=Mon Apr 19 18:42:06 CST 2021, time=2021-04-19, status=1, ipAttribution=)]
    2021-04-22 科研科研科研

    家庭聚集性研究

    0

  5. 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topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160806/IMG57A5698BDB0244113.jpg, createdBy=32a91358059, createdName=jyzxjiangqin, createdTime=Mon Apr 19 18:42:06 CST 2021, time=2021-04-19, status=1, ipAttribution=)]
  6. 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  7. 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    2021-04-21 一闲
  8. 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objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95069, encryptionId=007d9506920, topicName=遗传变异)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=73a3403, createdName=weihongyv, createdTime=Wed Apr 21 08:27:20 CST 2021, time=2021-04-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1408287, encodeId=3325140828eb6, content=<a href='/topic/show?id=92194628826' target=_blank style='color:#2F92EE;'>#宫颈#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46288, encryptionId=92194628826, topicName=宫颈)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=11102737131, createdName=一闲, createdTime=Wed Apr 21 08:27:20 CST 2021, time=2021-04-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1034275, encodeId=efe410342e50f, content=顶刊就是不一样,质量很高,内容精彩!学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=131, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=goodbing, createdTime=Mon Apr 19 20:27:20 CST 2021, time=2021-04-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1038251, encodeId=be791038251ba, content=谢谢梅斯分享这么多精彩信息, beContent=null, objectType=article, channel=null, level=null, likeNumber=147, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=anti-cancer, createdTime=Mon Apr 19 20:27:20 CST 2021, time=2021-04-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=958452, encodeId=421b958452c8, content=好文章!, beContent=null, objectType=article, channel=null, level=null, likeNumber=122, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160806/IMG57A5698BDB0244113.jpg, createdBy=32a91358059, createdName=jyzxjiangqin, createdTime=Mon Apr 19 18:42:06 CST 2021, time=2021-04-19, status=1, ipAttribution=)]
    2021-04-19 goodbing

    顶刊就是不一样,质量很高,内容精彩!学到很多

    0

  9. [GetPortalCommentsPageByObjectIdResponse(id=1831126, encodeId=d1a518311267e, content=<a href='/topic/show?id=1b6210686b2' target=_blank style='color:#2F92EE;'>#Lancet#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10686, encryptionId=1b6210686b2, topicName=Lancet)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3f0227, createdName=howi, createdTime=Sun Dec 19 11:27:20 CST 2021, time=2021-12-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1715809, encodeId=5a321e1580968, content=<a href='/topic/show?id=6f9f4631036' target=_blank style='color:#2F92EE;'>#宫颈癌前病变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46310, encryptionId=6f9f4631036, topicName=宫颈癌前病变)], attachment=null, authenticateStatus=null, createdAvatar=null, 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objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95069, encryptionId=007d9506920, topicName=遗传变异)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=73a3403, createdName=weihongyv, createdTime=Wed Apr 21 08:27:20 CST 2021, time=2021-04-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1408287, encodeId=3325140828eb6, content=<a href='/topic/show?id=92194628826' target=_blank style='color:#2F92EE;'>#宫颈#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46288, encryptionId=92194628826, topicName=宫颈)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=11102737131, createdName=一闲, createdTime=Wed Apr 21 08:27:20 CST 2021, time=2021-04-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1034275, encodeId=efe410342e50f, content=顶刊就是不一样,质量很高,内容精彩!学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=131, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=goodbing, createdTime=Mon Apr 19 20:27:20 CST 2021, time=2021-04-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1038251, encodeId=be791038251ba, content=谢谢梅斯分享这么多精彩信息, beContent=null, objectType=article, channel=null, level=null, likeNumber=147, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=anti-cancer, createdTime=Mon Apr 19 20:27:20 CST 2021, time=2021-04-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=958452, encodeId=421b958452c8, content=好文章!, beContent=null, objectType=article, channel=null, level=null, likeNumber=122, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160806/IMG57A5698BDB0244113.jpg, createdBy=32a91358059, createdName=jyzxjiangqin, createdTime=Mon Apr 19 18:42:06 CST 2021, time=2021-04-19, status=1, ipAttribution=)]
    2021-04-19 anti-cancer

    谢谢梅斯分享这么多精彩信息

    0

  10. 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content=顶刊就是不一样,质量很高,内容精彩!学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=131, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=goodbing, createdTime=Mon Apr 19 20:27:20 CST 2021, time=2021-04-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1038251, encodeId=be791038251ba, content=谢谢梅斯分享这么多精彩信息, beContent=null, objectType=article, channel=null, level=null, likeNumber=147, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=anti-cancer, createdTime=Mon Apr 19 20:27:20 CST 2021, time=2021-04-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=958452, encodeId=421b958452c8, content=好文章!, beContent=null, objectType=article, channel=null, level=null, likeNumber=122, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160806/IMG57A5698BDB0244113.jpg, createdBy=32a91358059, createdName=jyzxjiangqin, createdTime=Mon Apr 19 18:42:06 CST 2021, time=2021-04-19, status=1, ipAttribution=)]
    2021-04-19 jyzxjiangqin

    好文章!

    0

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