林奇综合征中MLH1,MSH2和MSH6基因的生殖基因突变与癌症风险相关
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
概括
林奇综合征的癌症风险因基因突变而异. MSH6突变带来较低的风险,而MLH1和MSH2突变带来更高的风险,特别是在40岁以后.
科学领域:
- 遗传学和基因组学 在
- 癌症流行病学 癌症流行病学
- 临床遗传学 临床遗传学
背景情况:
- 准确的癌症风险估计对于林奇综合征管理至关重要.
- 林奇综合征是一种遗传性疾病,增加了各种癌症的风险.
- 不匹配修复 (MMR) 基因 (MLH1,MSH2,MSH6) 的突变是主要原因.
研究的目的:
- 为了估计林奇综合征的家庭中特定年龄的累积癌症风险.
- 为了比较与MLH1,MSH2和MSH6基因突变相关的癌症风险.
- 为林奇综合征患者的临床管理和遗传咨询提供信息.
主要方法:
- 分析了来自40个法国癌症遗传学诊所的537个患有林奇综合征的家庭 (ERISCAM研究).
- 使用基因型限制可能性 (GRL) 方法来估计癌症风险.
- 考虑到统计分析中的确定偏差.
主要成果:
- 在MLH1,MSH2和MSH6突变载体中观察到累积癌症风险的显著差异 (P = .01).
- 到70岁时,估计结直肠癌风险为41% (MLH1),48% (MSH2) 和12% (MSH6).
- 在70岁时,子宫内膜癌的终身风险为54% (MLH1),21% (MSH2) 和16% (MSH6);卵巢癌的风险为20% (MLH1),24% (MSH2) 和1% (MSH6).
结论:
- 与MLH1或MSH2突变相比,MSH6突变与癌症风险明显降低.
- MLH1和MSH2突变对卵巢和子宫内膜癌的终身风险很高.
- 在MLH1/MSH2携带者中,这些风险在40岁以后才会显著增加.
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