Nat Commun:乳腺癌的多基因风险评估

2020-12-30 xiaozeng MedSci原创

在女性中,乳腺癌是最常被诊断出的癌症,也是癌症相关死亡的主要原因之一。除了由乳腺癌易感基因中的高风险突变引起的遗传易感性之外,乳腺癌还具有高度多基因的遗传模式。

在女性中,乳腺癌是最常被诊断出的癌症,也是癌症相关死亡的主要原因之一。除了由乳腺癌易感基因中的高风险突变引起的遗传易感性之外,乳腺癌还具有高度多基因的遗传模式。

迄今为止,大规模的基因筛查已鉴定了一百多个与乳腺癌风险相关的突变位点。这些变异以及其他的许多尚未被发现的变异,代表了通过广泛的分子通路起作用的常见遗传变异,而高风险乳腺癌易感性基因中的罕见的、高风险致病变异往往会破坏如保持DNA修复过程完整性的特定通路。


既往研究显示,乳腺癌的多基因风险评分(PRS)有可能改善患者的风险预测,但目前其在各种临床情况下效用的相关信息仍有限。

遗传风险的地理差异

在该研究中,研究人员旨在全面评估种系遗传变异对乳腺癌风险的影响。研究人员采用了FinnGen研究的数据,在收集的122978名女性中,有8401例的乳腺癌病例,通过PRS评分修改了两种高影响力的移码突变体的乳腺癌发病风险。


研究人员发现,在确诊乳腺癌后,PRS升高的患者患对侧乳腺癌的风险升高,且PRS可以极大的改善女性一级亲属的风险评估。更详细的研究显示,在携带PALB2 c.1592delT突变体的妇女(在芬兰中242倍富集,336名携带者)和平均PRS(10-90%百分位数)的妇女的终生患乳腺癌的风险为55%,而PRS评分高的(>第90个百分位数)风险升至84%(71-97%),PRS评分低的(<10个百分位数)风险降至49%(30-68%)。

PALB2和CHEK2突变携带者的多基因风险评估

同样的,携带CHEK2 c.1100delC突变(3.7倍富集,1648个携带者),的各评分患病风险分别为29%(27-32%)、59%(52-66%)和9%(5-14%)。同时,PRS还完善了一级亲属患有乳腺癌的女性被诊断出患有乳腺癌的风险评估,尤其是那些有早发性乳腺癌阳性家族史的女性。


综上,该研究结果以综合方式评估了普通人群、乳腺癌患者和未受影响家庭成员的乳腺癌遗传风险


原始出处:

Mars, N., Widén, E., Kerminen, S. et al. The role of polygenic risk and susceptibility genes in breast cancer over the course of life. Nat Commun 11, 6383 (14 December 2020).

 

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    2021-02-21 liuli5079
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    2021-05-13 syscxl
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  5. [GetPortalCommentsPageByObjectIdResponse(id=2087864, encodeId=24d4208e864ae, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Sun Feb 21 02:15:25 CST 2021, time=2021-02-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1754456, encodeId=fe8b1e544560d, content=<a href='/topic/show?id=44e2431e1c6' target=_blank style='color:#2F92EE;'>#多基因#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43171, encryptionId=44e2431e1c6, topicName=多基因)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b34b36693912, createdName=syscxl, createdTime=Thu May 13 11:15:25 CST 2021, time=2021-05-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1704508, encodeId=6bb61e04508fa, content=<a href='/topic/show?id=1f5b41931ce' target=_blank style='color:#2F92EE;'>#基因风险#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41931, encryptionId=1f5b41931ce, topicName=基因风险)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cb0530750602, createdName=hmwwww, createdTime=Thu Jan 07 10:15:25 CST 2021, time=2021-01-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1949770, encodeId=46cf1949e70ea, content=<a href='/topic/show?id=b1ec431e5ab' target=_blank style='color:#2F92EE;'>#多基因风险#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43175, encryptionId=b1ec431e5ab, topicName=多基因风险)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c49e75, createdName=qjddjq, createdTime=Wed Sep 01 09:15:25 CST 2021, time=2021-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1884876, encodeId=787818848e65d, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sat May 29 20:15:25 CST 2021, time=2021-05-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=912381, encodeId=1fc591238111, content=<a href='/topic/show?id=73c423e2572' target=_blank style='color:#2F92EE;'>#乳腺癌#</a>还需要更多的数据更长的随访时间和结论, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23725, encryptionId=73c423e2572, topicName=乳腺癌)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200627/83a502bff6c14b759a7d0863b4068e7b/32ad40676056418ea58a94afac9c5b81.jpg, createdBy=6f475314305, createdName=水-晶, createdTime=Wed Dec 30 23:27:07 CST 2020, time=2020-12-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=912272, encodeId=fb1a9122e2d2, content=<a href='/topic/show?id=73c423e2572' target=_blank style='color:#2F92EE;'>#乳腺癌#</a>研究越来越透彻了, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23725, encryptionId=73c423e2572, topicName=乳腺癌)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220301/6252e946e5ef413b86dc0f7d1f73b6db/9a7e8c88a38e487b8da4968a67bbd261.png, createdBy=b9f692910, createdName=rayms, createdTime=Wed Dec 30 18:34:39 CST 2020, time=2020-12-30, status=1, ipAttribution=)]
    2021-05-29 liye789132251
  6. [GetPortalCommentsPageByObjectIdResponse(id=2087864, encodeId=24d4208e864ae, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Sun Feb 21 02:15:25 CST 2021, time=2021-02-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1754456, encodeId=fe8b1e544560d, content=<a href='/topic/show?id=44e2431e1c6' target=_blank style='color:#2F92EE;'>#多基因#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43171, encryptionId=44e2431e1c6, topicName=多基因)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b34b36693912, createdName=syscxl, createdTime=Thu May 13 11:15:25 CST 2021, time=2021-05-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1704508, encodeId=6bb61e04508fa, content=<a href='/topic/show?id=1f5b41931ce' target=_blank style='color:#2F92EE;'>#基因风险#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41931, encryptionId=1f5b41931ce, topicName=基因风险)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cb0530750602, createdName=hmwwww, createdTime=Thu Jan 07 10:15:25 CST 2021, time=2021-01-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1949770, encodeId=46cf1949e70ea, content=<a href='/topic/show?id=b1ec431e5ab' target=_blank style='color:#2F92EE;'>#多基因风险#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43175, encryptionId=b1ec431e5ab, topicName=多基因风险)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c49e75, createdName=qjddjq, createdTime=Wed Sep 01 09:15:25 CST 2021, time=2021-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1884876, encodeId=787818848e65d, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sat May 29 20:15:25 CST 2021, time=2021-05-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=912381, encodeId=1fc591238111, content=<a href='/topic/show?id=73c423e2572' target=_blank style='color:#2F92EE;'>#乳腺癌#</a>还需要更多的数据更长的随访时间和结论, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23725, encryptionId=73c423e2572, topicName=乳腺癌)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200627/83a502bff6c14b759a7d0863b4068e7b/32ad40676056418ea58a94afac9c5b81.jpg, createdBy=6f475314305, createdName=水-晶, createdTime=Wed Dec 30 23:27:07 CST 2020, time=2020-12-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=912272, encodeId=fb1a9122e2d2, content=<a href='/topic/show?id=73c423e2572' target=_blank style='color:#2F92EE;'>#乳腺癌#</a>研究越来越透彻了, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23725, encryptionId=73c423e2572, topicName=乳腺癌)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220301/6252e946e5ef413b86dc0f7d1f73b6db/9a7e8c88a38e487b8da4968a67bbd261.png, createdBy=b9f692910, createdName=rayms, createdTime=Wed Dec 30 18:34:39 CST 2020, time=2020-12-30, status=1, ipAttribution=)]
    2020-12-30 水-晶

    #乳腺癌#还需要更多的数据更长的随访时间和结论

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=2087864, encodeId=24d4208e864ae, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Sun Feb 21 02:15:25 CST 2021, time=2021-02-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1754456, encodeId=fe8b1e544560d, content=<a href='/topic/show?id=44e2431e1c6' target=_blank style='color:#2F92EE;'>#多基因#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43171, encryptionId=44e2431e1c6, topicName=多基因)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b34b36693912, createdName=syscxl, createdTime=Thu May 13 11:15:25 CST 2021, time=2021-05-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1704508, encodeId=6bb61e04508fa, content=<a href='/topic/show?id=1f5b41931ce' target=_blank style='color:#2F92EE;'>#基因风险#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41931, encryptionId=1f5b41931ce, topicName=基因风险)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cb0530750602, createdName=hmwwww, createdTime=Thu Jan 07 10:15:25 CST 2021, time=2021-01-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1949770, encodeId=46cf1949e70ea, content=<a href='/topic/show?id=b1ec431e5ab' target=_blank style='color:#2F92EE;'>#多基因风险#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43175, encryptionId=b1ec431e5ab, topicName=多基因风险)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c49e75, createdName=qjddjq, createdTime=Wed Sep 01 09:15:25 CST 2021, time=2021-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1884876, encodeId=787818848e65d, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sat May 29 20:15:25 CST 2021, time=2021-05-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=912381, encodeId=1fc591238111, content=<a href='/topic/show?id=73c423e2572' target=_blank style='color:#2F92EE;'>#乳腺癌#</a>还需要更多的数据更长的随访时间和结论, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23725, encryptionId=73c423e2572, topicName=乳腺癌)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200627/83a502bff6c14b759a7d0863b4068e7b/32ad40676056418ea58a94afac9c5b81.jpg, createdBy=6f475314305, createdName=水-晶, createdTime=Wed Dec 30 23:27:07 CST 2020, time=2020-12-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=912272, encodeId=fb1a9122e2d2, content=<a href='/topic/show?id=73c423e2572' target=_blank style='color:#2F92EE;'>#乳腺癌#</a>研究越来越透彻了, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23725, encryptionId=73c423e2572, topicName=乳腺癌)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220301/6252e946e5ef413b86dc0f7d1f73b6db/9a7e8c88a38e487b8da4968a67bbd261.png, createdBy=b9f692910, createdName=rayms, createdTime=Wed Dec 30 18:34:39 CST 2020, time=2020-12-30, status=1, ipAttribution=)]
    2020-12-30 rayms

    #乳腺癌#研究越来越透彻了

    0

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