胃と腸43巻13号

2008年12月発行

今月の主題 大腸癌の発生・発育進展

主題

大腸癌における分子異常

著者： 菅井有¹ 幅野渉²

所属機関： ¹岩手医科大学医学部病理学講座分子診断病理学分野 ²岩手医科大学薬学部薬物代謝動態学講座

ページ範囲：P.1965 - P.1974

文献概要

要旨　大腸癌は多段階発癌の代表的モデルで，これに関連して多くの遺伝子異常の仮説が提唱されてきた．ゲノムレベルの異常としては，CINとMSI（MIN）がある．これに加えて，遺伝子のプロモーター領域のメチル化が大腸癌の発生に重要なことが指摘されてきた．これはCpG island methylation phenotypeと言われ，MSIやki-ras変異に関連している．細胞周期の異常からも大腸癌発生のメカニズムが明らかになっている．Wnt系経路，ki-ras系経路，TGFβ系経路，p53系経路のいずれか，もしくは複数の経路に異常が蓄積されている．大腸癌の組織発生としては，腺腫を経由するタイプがほとんどで，これにはAPC，ki-ras，p53遺伝子の変異が密接に関連している．一方，正常粘膜から直接発癌するde novo型発癌も指摘され，これにはp53遺伝子変異が関与しているとされる．その他，鋸歯状病変や炎症性背景を基に発生することも明らかになっており，大腸癌は最も分子レベルの異常が明らかになっている癌である．

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