Prospective determination of prevalence of lynch syndrome in young women with endometrial cancer
Prospective determination of prevalence of lynch syndrome in young women with endometrial cancer
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DOI：
10.1200/jco.2007.10.8597
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发表时间：
2007-11-20
影响因子：
45.3
通讯作者：
Broaddus, Russell R.
中科院分区：
文献类型：
--
作者：
Lu, Karen H.;Schorge, John O.;Broaddus, Russell R.
目的：结肠癌诊断时年龄小于50岁常被用作Lynch综合征（遗传性非息肉病性结直肠癌综合征）的筛查标准。本研究的目的是确定MLH 1，MSH 2和MSH 6突变的患病率在一个队列的妇女诊断为子宫内膜癌在年龄小于50 years.Methods一个前瞻性的，多中心的研究进行了三个机构。获得书面同意后，通过MLH 1、MSH 2和MSH 6基因的全测序和大缺失分析进行种系突变检测。肿瘤研究包括MLH 1，MSH 2和MSH 6的免疫组化;微卫星不稳定性分析;和MLH 1 promoter.Results的超甲基化的100名妇女，9（9%; 95%CI 4.2至16.4）进行了有害的生殖系突变：7名妇女与MSH 2突变，一名妇女与MLH 1突变，和一名妇女与MSH 6突变。另外两名女性的分子研究与Lynch综合征的诊断一致。整个队列的平均体重指数（BMI）为34.4，显著高于突变携带者的平均BMI 29.2。发现生殖系突变的预测因素包括一级亲属与林奇综合征相关的癌症，子宫内膜肿瘤与MSH 2表达的损失，肿瘤与高微卫星不稳定性，和较低的BMI.Conclusion在这项前瞻性研究中，年龄小于50岁的子宫内膜癌患者，9%被发现携带生殖系林奇综合征相关的突变。除了年轻的发病年龄，家族史，BMI和分子肿瘤研究可以提高识别MLH 1，MSH 2和MSH 6中Lynch综合征相关生殖系突变的可能性。
Purpose Age younger than 50 years at the time of colon cancer diagnosis is often used as a screening criterion for Lynch syndrome (hereditary nonpolyposis colorectal cancer syndrome). The purpose of this study was to determine the prevalence of MLH1, MSH2, and MSH6 mutations in an unselected cohort of women diagnosed with endometrial cancer at age younger than 50 years.Methods A prospective, multicenter study was performed at three institutions. After written consent was obtained, germline mutation testing by full sequencing and large deletion analysis of the MLH1, MSH2, and MSH6 genes was performed. Tumor studies included immunohistochemistry of MLH1, MSH2, and MSH6; microsatellite instability analysis; and hypermethylation of the MLH1 promoter.Results Of the 100 women, nine (9%; 95% CI 4.2 to 16.4) carried a deleterious germline mutation: seven women with mutations in MSH2, one woman with a mutation in MLH1, and one woman with a mutation in MSH6. Two additional women had molecular studies consistent with the diagnosis of Lynch syndrome. The mean body mass index (BMI) for the entire cohort was 34.4, which is significantly higher than 29.2, the mean BMI for the mutation carriers. Predictors of finding a germline mutation included having a first-degree relative with a Lynch syndrome - associated cancer, endometrial tumor with loss of MSH2 expression, tumors with high microsatellite instability, and lower BMI.Conclusion In this prospective study of endometrial cancer patients younger than age 50 years, 9% were found to carry germline Lynch syndrome - associated mutations. In addition to young age of onset, family history, BMI, and molecular tumor studies can improve the likelihood of identifying a Lynch syndrome - associated germline mutation in MLH1, MSH2, and MSH6.