Prospective Determination of Prevalence of Lynch Syndrome in Young Women With Endometrial Cancer

作者：Karen H. Lu, John O. Schorge, Kerry J. Rodabaugh, Molly S. Daniels, Charlotte C. Sun, Pamela T. Soliman, Kristin G. White, Rajyalakshmi Luthra, David Marc Gershenson, Russell R. Broaddus · 发表于：Journal of Clinical Oncology · 年份：2007 · DOI：10.1200/jco.2007.10.8597 · 被引用次数：259 · 研究领域：Genetic factors in colorectal cancer、Endometrial and Cervical Cancer Treatments、Colorectal Cancer Screening and Detection

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 pati...