遺伝的な拡散性胃がんの家族における創始者および再発性CDH1変異
Pardeep Kaurah1, Andrée MacMillan, Niki Boyd
1Hereditary Cancer Program, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
JAMA
|June 5, 2007
まとめ
遺伝的拡散性胃がんのファミリーにおける再発性CDH1変異は,新しいイベントと共通の祖先の両方から生じます. ニューファンドランドの創始者変異が強く示され,胃がんと乳がんのリスクに影響を与えます.
科学分野:
- 遺伝学とゲノミクス
- がん生物学 がん生物学
- エピデミオロジー エピデミオロジー
背景:
- 遺伝性拡散性胃がん (HDGC) は,上皮カデリン (CDH1) 遺伝子の生殖線変異と関連しています.
- HDGCは,拡散性胃がんと乳癌のリスクを大幅に高めます.
研究 の 目的:
- 繰り返し発生する生殖系CDH1変異が,独立した変異イベントまたは共通の祖先から生じたかどうかを調査する.
- HDGCを持つ家族におけるCDH1変異の起源を特定する.
主な方法:
- CDH1変異の遺伝的拡散性胃がんを患った38の家族の分析.
- ハップロタイプ分析は14の家族 (本研究から7つ,以前報告された7つ) で実施され,再発性突然変異の共通の祖先を評価しました.
主要な成果:
- CDH1の変異は13種類あり,そのうち6種類は新型で,15のファミリー (40%の検出率) で発見されました.
- 特定の変異 (1137G>A,1901C>T,2064-2065delTG) は,共通の起源と独立した起源の両方の証拠を示しました.
- 創始者変異 (2398delC) は,ニューファンドランド出身の4つの家族で特定され,75歳までに胃がん (男性40%,女性63%) と乳がん (女性52%) の累積リスクが顕著でした.
結論:
- HDGCファミリーの再発性CDH1変異は,独立した出来事と共通の祖先の両方に起因する.
- 強力な証拠は,ニューファンドランド発祥の創始者変異を支持し,罹患した家族の癌リスクに影響を与えています.
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