リンチ症候群におけるMLH1,MSH2,MSH6遺伝子の生殖線変異に関連した癌のリスク
Valérie Bonadona1, Bernard Bonaïti, Sylviane Olschwang
1Université Lyon 1, Centre National de la Recherche Scientifique UMR5558, Villeurbanne, Centre Léon Bérard, Lyon, Cedex 08, France.
JAMA
|June 7, 2011
まとめ
リンチ症候群の癌のリスクは,遺伝子変異によって大きく異なります. MSH6変異はリスクが低く,MLH1およびMSH2変異はリスクが高く,特に40歳以降に発生する.
科学分野:
- 遺伝学とゲノミクス
- 癌の流行病学について
- 臨床遺伝学 臨床遺伝学とは
背景:
- 癌のリスクの正確な推定は,リンチ症候群の管理に不可欠です.
- リンチ症候群は,様々な癌のリスクを増やす遺伝疾患です.
- 不一致修復 (MMR) 遺伝子 (MLH1,MSH2,MSH6) の変異が主な原因である.
研究 の 目的:
- リンチ症候群の家族における年齢特有の累積的ながんリスクを推定する.
- MLH1,MSH2,MSH6遺伝子の突然変異に関連するがんリスクを比較する.
- リンチ症候群の患者の臨床管理と遺伝カウンセリングの情報提供.
主な方法:
- リンチ症候群の537家族を40のフランスのがん遺伝学クリニックから分析した (ERISCAM研究).
- 遺伝子型限定確率 (GRL) 方法を用いてがんリスクを推定した.
- 統計分析における確定バイアスを考慮した.
主要な成果:
- MLH1,MSH2およびMSH6変異媒介者の間で累積的ながんリスクの有意な差異が観察されました (P = .01).
- 70歳までに推定された結腸直腸がんリスクは41% (MLH1),48% (MSH2),12% (MSH6) であった.
- 70歳までの子宮内膜がんの生涯リスクは54% (MLH1),21% (MSH2) および16% (MSH6) であった;卵巣がんのリスクは20% (MLH1),24% (MSH2) および1% (MSH6) であった.
結論:
- MSH6変異は,MLH1またはMSH2変異と比較して,癌のリスクが大幅に低下します.
- MLH1およびMSH2変異は,卵巣および子宮内膜がんの生涯リスクが高い.
- これらのリスクは,MLH1/MSH2のキャリアの40歳以降まで有意に増加しません.
関連する概念動画
Mismatch Repair
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
Mismatch Repair
Overview
Cancer Prevention
Several factors can increase the risk of cancer in an individual. About 50% of cancer cases can be prevented by adopting a healthy lifestyle, regular exercise, eating healthy, and following a modest cancer prevention diet. Epidemiological studies have consistently shown that populations with vegetable and fruit-rich diets have reduced the incidence of cancer. On the other hand, populations who have a diet rich in animal fat, red meat, junk food, or high calories are predisposed to cancer.
Some...
Some...
Cancers Originate from Somatic Mutations in a Single Cell
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
Cancers Originate from Somatic Mutations in a Single Cell
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...

