Lancet oncol:未知因素明显影响林奇综合征患者罹患结直肠癌的风险

2021-06-08 MedSci原创 MedSci原创

林奇综合征患者之间发生结直肠癌的风险仍存在很大差异,不能以一言概之

针对 DNA 错配修复基因致病性变异(林奇综合征)携带者的现有临床实践指南是基于同一基因中所有致病变异携带者的结直肠癌平均年龄特异性累积风险(外显率)。

本研究旨在估计相同基因致病性变异携带者之间结直肠癌外显率的差异

这是一项回顾性队列研究,从国际错配修复联盟获取数据,该联盟由来自六大洲32个国家的122个研究中心或诊所的273名成员组成,致力于林奇综合征研究。本次分析纳入了至少有三位成员且至少一位成员确诊为DNA错配修复基因(MLH1、MSH2、MSH6 或 PMS2)致病性或可能致病性变异携带者的家庭。排除具有已知新发致病性变异的先证者家族。

来自22个国家的5585个林奇综合征家庭符合本次分析条件。其中,没有足够的数量来估计亚洲和南美洲以及EPCAM变异的外显率。因此,研究人员采用了于2014年7月11日-2018年12月31日期间从北美、欧洲和澳大拉西亚的15个国家收集的5255个家庭(1829例MLH1、2179例MSH2、798例MSH6和449例PMS2)的数据,共涵盖79809位亲属。

不同分组的林奇综合征患者发生结直肠癌的累积风险

强有力的证据表明,存在未知的家族风险因素能够改变林奇综合征患者的结直肠癌风险(p<0.0001)。这些家族性风险因素导致来自各大洲的携带相同基因或 MSH2 c.942+3A>T 变异的男性和女性罹患结直肠癌的风险存在广泛的异质性。

不同基因变异携带者的结直肠癌风险比

这种异质性在MLH1和MSH2变异携带者中尤为明显,且与基因、性别和地区相关,约7-56%的MLH1或MSH2变异携带者的结直肠癌外显率<20%,9-44%的携带者的结直肠癌外显率>80%,只有10-19%的携带者的结直肠癌外显率为40-60%

该研究结果强调了风险校正的重要作用,有助于推进个性化风险评估,从而进行精准预防和早期发现林奇综合征患者发生了结直肠癌。

简言之,林奇综合征患者之间发生结直肠癌的风险仍存在很大差异,不能以一言概之。不过,虽然部分林奇综合征患者的结直肠癌外显率相对较低,但还高于普通人群。

原始出处:

The International Mismatch Repair Consortium. Variation in the risk of colorectal cancer in families with Lynch syndrome: a retrospective cohort study. June 07, 2021. https://doi.org/10.1016/S1470-2045(21)00189-3

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  1. [GetPortalCommentsPageByObjectIdResponse(id=1831205, encodeId=c4e51831205d3, content=<a href='/topic/show?id=1b6210686b2' target=_blank style='color:#2F92EE;'>#Lancet#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10686, encryptionId=1b6210686b2, topicName=Lancet)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3f0227, createdName=howi, createdTime=Sat Jul 24 03:14:22 CST 2021, time=2021-07-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=974890, encodeId=42b99e4890bf, content=有用, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/4PrW5Wlg2MPQDFZtgjSfKzzZKpicHicUFY2ebicqW2yBzib12icU11Djrbj4lsI4bZXJKbt2QEUlAndjNE1Rd5ka7qA/132, createdBy=fc685321753, createdName=gr, createdTime=Sat Jun 19 15:48:12 CST 2021, time=2021-06-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1866109, encodeId=8dd818661093f, content=<a href='/topic/show?id=16ce133504e' target=_blank style='color:#2F92EE;'>#Oncol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13350, encryptionId=16ce133504e, topicName=Oncol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b63894, createdName=minlingfeng, createdTime=Wed Jul 14 23:14:22 CST 2021, time=2021-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1432072, encodeId=004114320e2dc, content=<a href='/topic/show?id=f9b9e9124a8' target=_blank style='color:#2F92EE;'>#综合征#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79124, encryptionId=f9b9e9124a8, topicName=综合征)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Thu Jun 10 13:14:22 CST 2021, time=2021-06-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1453524, encodeId=598314535246b, content=<a href='/topic/show?id=098ee8679ad' target=_blank style='color:#2F92EE;'>#结直肠#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78679, encryptionId=098ee8679ad, topicName=结直肠)], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=9ace5575596, createdName=crystal0564, createdTime=Thu Jun 10 13:14:22 CST 2021, time=2021-06-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1034354, encodeId=82511034354f0, 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=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=goodbing, createdTime=Wed Jun 09 01:14:22 CST 2021, time=2021-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1038313, encodeId=4c1710383131d, content=谢谢梅斯分享这么多精彩信息, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=anti-cancer, createdTime=Wed Jun 09 01:14:22 CST 2021, time=2021-06-09, status=1, ipAttribution=)]
    2021-07-24 howi
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    2021-06-19 gr

    有用

    0

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    2021-07-14 minlingfeng
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    2021-06-09 goodbing

    顶刊就是不一样,质量很高,内容精彩!学到很多

    0

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    2021-06-09 anti-cancer

    谢谢梅斯分享这么多精彩信息

    0

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