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JAMA Oncology:吸烟致癌?颊粘膜拭子一刮就知道!

2015-05-18 MedSci MedSci原创

最新发表在JAMA Oncology杂志上的研究显示,吸烟所引起的DNA损伤可以通过颊粘膜拭子检测到。这项研究为吸烟所导致癌症产生所经历的一般程序提供了证据支持,而这一现象也出现在与吸烟通常被认为没有关联的癌症,包括乳腺癌和妇科癌症。该项由UCL妇女健康协会的妇女肿瘤部主任Martin Widschwendter教授以及伦敦大学的Andrew Teschendorff博士所领导的研究团队着眼于表观

最新发表在JAMA Oncology杂志上的研究显示,吸烟所引起的DNA损伤可以通过颊粘膜拭子检测到。这项研究为吸烟所导致癌症产生所经历的一般程序提供了证据支持,而这一现象也出现在与吸烟通常被认为没有关联的癌症,包括乳腺癌和妇科癌症。

该项由UCL妇女健康协会的妇女肿瘤部主任Martin Widschwendter教授以及伦敦大学的Andrew Teschendorff博士所领导的研究团队着眼于表观遗传改变——开启或关闭基因表达的DNA改变。表观遗传变异与癌症发展密切相关,而前者可能与暴露于香烟烟雾等环境因素相关。

研究人员旨在探索颊粘膜的正常细胞是否会证明表观遗传变化与肺癌和其他上皮癌有关。这些类型的癌症起源于上皮细胞——如皮肤覆盖身体的外面或如粘膜覆盖身体器官和体腔内壁,该类型癌症占英国所有癌症病例的85%。从颊粘膜拭子中很容易收集颊细胞,而后者则直接暴露于吸烟者的香烟烟雾中。

研究人员分析了1946年出生的790名女性的颊粘膜拭子样本以及152例配对的血液样本,该数据来自英国医学研究理事会国家卫生与发展调查委员会。数据集还包含了吸烟史以及收集样本时的吸烟状况。

这一分析表明,吸烟女性的颊粘膜细胞存在很多改变表观基因改变——被称为DNA甲基化(DNAme)。 相比对应的血液样本,吸烟者的颊细胞的异常甲基化会增加40倍,这一差异使它们的DNA变化更可靠。

研究团队接着在5000多个组织样本中分析这种吸烟引起的表观遗传变化过程,包括正常组织、癌前病变组织以及从15个种不同的上皮癌的组织。他们试图在测试过程中区分癌组织和正常组织。他们发现这个发展过程——最初在吸烟者正常颊细胞开始衍生的,能够100%敏感性区分正常和癌组织的,100%特异性出现在发生癌症的器官中。

研究人员还发现,这个变化程序的缺失或存在能够预测前进展性癌症病变的命运。细胞中有缺陷程序的存在很有可能促使前进展性癌症进展到完全进展性癌症。然而,这种缺陷程序的消失则有可能使得癌前病变的发展受抑制,甚至消失。

作者Andrew Teschendorff(伦敦大学癌症研究所)说:“我们的工作表明,吸烟对正常细胞的表观基因组产生重大影响是形同直接暴露于致癌物。具有特别意义的是,这些表观遗传变化也出现与吸烟相关或不想过的癌症中,这意味着是一个普遍的癌症发生过程。这项研究让我们更接近并理解第一步骤致癌作用,以及在未来可能会为我们提供急需的风险预测和早期检测手段。”


原始出处:
Andrew E. Teschendorff, Zhen Yang, Andrew Wong, Christodoulos P. Pipinikas, Yinming Jiao, Allison Jones, Shahzia Anjum, Rebecca Hardy, Helga B. Salvesen, Christina Thirlwell, Samuel M. Janes, Diana Kuh, Martin Widschwendter. Correlation of Smoking-Associated DNA Methylation Changes in Buccal Cells With DNA Methylation Changes in Epithelial Cancer. JAMA Oncology, 2015; DOI:10.1001/jamaoncol.2015.1053

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    2015-10-26 minlingfeng
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    2015-11-09 guoyibin
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    2015-05-21 cement123

    这么厉害

    0

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    2015-05-20 jambiya

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