大腸がんにおける変異過程における地理的および年齢的変動

Marcos Díaz-Gay^1,2,3,4, Wellington Dos Santos⁵, Sarah Moody⁶

¹Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.

Nature

|April 23, 2025

まとめ

特にコリバクチンを産生する細菌による変異過程は地域的に異なっており,早期発症の結腸直腸がんの発生率の増加と関連しています. この暴露は早期の腫瘍発症とAPC変異を誘発する可能性があります.

科学分野:

ゲノミクス
癌研究
微生物学

背景:

結腸直腸がんの発生率は地域によって異なるが,最近では早期発症 (50歳未満) の症例が倍増している.
早期発症の結腸直腸癌の発生率の増加の根本的な原因はほとんど不明です.

研究の目的:

大腸がんにおける地理的および年齢による差異に対する変異過程の寄与を調査する.
特定の変異シグネチャーとその潜在的な環境または微生物の起源を特定する.

主な方法:

11カ国から98"人の結腸直腸がん患者のゲノム解析
ミクロサテライト安定型とミクロサテライト不安定型がんにおける変異負荷とシグネチャの比較
地理的な位置,発症年齢,ドライバー変異との特定の変異シグネチャーの関連分析.

主要な成果:

マイクロサテライトに安定した結腸直腸がんでは,異なった国で突然変異の負荷とシグネチャーの有意な変動が見られた.
バクテリアの変異因子であるコリバクチンに関連したSBS88およびID18の変異シグネチャーは,大腸がんの発生率が高い国においてより一般的であった.
これらのコリバクチン関連シグネチャーは,早期発症の結腸直腸がんにおいて有意に濃縮され,APCドライバー変異と関連していました.

結論:

大腸がんの変異過程には,変異因子の曝露の影響で地理的な違いがある.
コリバクチンを産生するバクテリアへの曝露は,早期発症の結腸直腸がんの発生率増加に寄与する要因である可能性があります.
コリバクチンの変異シグネチャーは,大腸がんにおけるAPCドライバー変異の発生に作用する.

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