空気汚染物質による肺腺がんの促進
William Hill1, Emilia L Lim1,2, Clare E Weeden1
1Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
Nature
|April 5, 2023
まとめ
空気汚染,特に微細粒子 (PM2.5) は,肺細胞の既にある変異を活性化することによって,肺がんを促進します. この研究は,空気の質と癌の発生を関連付け,公衆衛生対策を促しています.
科学分野:
- 環境 健康
- 腫瘍学
- 分子生物学
背景:
- 癌を誘発する環境への曝露のメカニズムは まだ十分に理解されていません
- 腫瘍創生は伝統的に遺伝子変異と後続的な増殖を含む多段階のプロセスとして見られています.
- 空気汚染,特にPM2.5は肺がんの危険因子として知られています.
研究 の 目的:
- 肺がんの促進におけるPM2.5の役割,特にEGFR主導の症例を調査する.
- PM2.5 曝露が肺腫瘍形成を誘発または促進する細胞および分子メカニズムを解明する.
- ヒストロジカルに正常な肺組織における腫瘍誘発変異の有病率を決定する.
主な方法:
- 大規模なコホート (32,957例) の分析で,PM2.5レベルとEGFR誘導肺がんの発生率を相関させました.
- 空気の汚染物質が肺組織に及ぼす生物学的影響を研究するために,機能的なマウスモデルを使用する.
- 3つのコホートで295人の正常な肺組織に 超深層変異プロファイリングを行いました
主要な成果:
- 高いPM2.5レベルとEGFR誘発性肺癌の発生率の増加との間に有意な関連性が見られた.
- マウスモデルでのPM2.5曝露は,マクロファージの流入,IL- 1βの放出,EGFR変異性肺細胞の原始細胞状態を誘発した.
- 既にある腫瘍性変異 (EGFR 18%, KRAS 53%) は,健康な肺組織サンプルの大部分で検出されました.
結論:
- PM2.5は腫瘍促進剤として作用し,既存の腫瘍変異を有する肺細胞を標的とする.
- 肺がんの発生と大気汚染の間の重要な関連が示され 2段階の腫瘍発生モデルが支持されています
- 大気汚染の削減は 肺がんの世界的な負担を軽減するために 極めて重要です
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