臨床婦人科産科64巻12号

2010年12月発行

今月の臨床 子宮体癌診療の動向─これだけは知っておきたい

子宮体癌発生のリスク因子

著者： 長谷川清志¹ 鳥居裕¹ 加藤利奈¹ 宇田川康博¹

所属機関： ¹藤田保健衛生大学産婦人科

ページ範囲：P.1605 - P.1615

文献概要

はじめに

　子宮体癌は発癌機構により主にタイプIとタイプIIとに分類される^1）．それらのタイプの発癌分子機構および関連因子および関連遺伝子の概略を図1に示した．タイプIはエストロゲン依存性で，プロゲステロンによる拮抗を受けないいわゆる“unopposed estrogen”が関与し，子宮内膜増殖症を前癌病変として発症する．比較的若年者に好発し，類内膜腺癌で高分化型が多く，PTENやK-ras遺伝子が関与し，比較的予後良好である．一方，タイプIIはエストロゲン非依存性で，比較的高齢女性に多く，p53遺伝子変異などにより萎縮内膜よりEIC（endometrial intraepithelial carcinoma）を経て漿液性腺癌が発生する．そのほか，低分化型類内膜腺癌，明細胞腺癌あるいは未分化癌などが発生し，予後不良のことが多い．

　発癌に関与する因子としては，主に環境因子，遺伝子因子，遺伝的因子などに分類される．環境因子はそのほとんどがエストロゲン（unopposed estrogen）と直接的あるいは間接的に関連している．遺伝子因子としてはタイプIの発癌初期の遺伝子変化としてDNAミスマッチ修復遺伝子（MMR遺伝子），PTENやK-rasなどの遺伝子変化が挙げられ，大腸癌と同様の多段階発癌モデルが提唱されている．また，タイプIIではp53遺伝子変異が多く認められるが，これらの変化に関与する因子は完全には解明されていない．さらに遺伝的因子としては，Lynch症候群に認められるMMR遺伝子異常が挙げられる．遺伝子因子とそれによる発癌分子機構に関しては他稿に譲り，ここでは，環境因子，遺伝的因子に関して概説する．

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