ヒトがんにおけるタバコ喫煙に関連する変異シグネチャー

Ludmil B Alexandrov^1,2,3, Young Seok Ju⁴, Kerstin Haase⁵

¹Theoretical Biology and Biophysics (T-6), Los Alamos National Laboratory, Los Alamos, NM 87545, USA. lba@lanl.gov mrs@sanger.ac.uk.

Science (New York, N.Y.)

|November 5, 2016

まとめ

タバコの喫煙は体内の変異量を増やすことで癌のリスクが高まります 5243種類の癌の分析により DNAの損傷や編集過程を含む喫煙に関連した異なった変異のサインが明らかになりました

科学分野:

腫瘍学
遺伝学
分子生物学

背景:

タバコの喫煙は人間の多くの癌の主要な危険因子です.
喫煙と癌を結びつける分子メカニズムを理解することは予防と治療に不可欠です

研究の目的:

タバコの喫煙と体内の変異と喫煙関連の癌におけるDNAメチル化との関連を調査する.
喫煙に起因する突然変異の特徴を特定し特徴づけること

主な方法:

5243個の癌サンプルから得られた体内の変異とDNAメチル化データの分析.
異なるがんの異なる変異シグネチャーの識別と比較.
タバコの致癌物質の直接的または間接的な影響と変異パターンの相関.

主要な成果:

喫煙は複数の異なる変異シグネチャーで変異負荷の増加と関連しています.
直接接触した組織に多く見られる一つの特徴はタバコの発がん物質によるDNA損傷によるものです
他のシグネチャーには,APOBECによるDNA編集と内生的な時計のようなプロセスが含まれています.
DNAメチル化における制限された差異は,喫煙に関連して観察された.

結論:

この発見は,喫煙が体内の変異量を増やすことで癌のリスクを増やすという仮説を裏付けている.
特定の変異シグネチャは喫煙が腫瘍形成を促す分子経路の洞察を与えてくれます
喫煙に関連する特定の癌については,まだ突然変異の負荷メカニズムに関する直接的な証拠が必要である.

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