Ramsoekh Dewkoemar, Wagner Anja, van Leerdam Monique E, Dooijes Dennis, Tops Carli Mj, Steyerberg Ewout W, Kuipers Ernst J
Department of Gastroenterology and Hepatology Erasmus MC University Medical Center, PO Box 2040, 3000 CA, Rotterdam, the Netherlands.
Hered Cancer Clin Pract. 2009 Dec 23;7(1):17. doi: 10.1186/1897-4287-7-17.
Lynch syndrome (LS) is associated with a high risk for colorectal cancer (CRC) and extracolonic malignancies, such as endometrial carcinoma (EC). The risk is dependent of the affected mismatch repair gene. The aim of the present study was to calculate the cumulative risk of LS related cancers in proven MLH1, MSH2 and MSH6 mutation carriers.
The studypopulation consisted out of 67 proven LS families. Clinical information including mutation status and tumour diagnosis was collected. Cumulative risks were calculated and compared using Kaplan Meier survival analysis.
MSH6 mutation carriers, both males and females had the lowest risk for developing CRC at age 70 years, 54% and 30% respectively and the age of onset was delayed by 3-5 years in males. With respect to endometrial carcinoma, female MSH6 mutation carriers had the highest risk at age 70 years (61%) compared to MLH1 (25%) and MSH2 (49%). Also, the age of EC onset was delayed by 5-10 years in comparison with MLH1 and MSH2.
Although the cumulative lifetime risk of LS related cancer is similar, MLH1, MSH2 and MSH6 mutations seem to cause distinguishable cancer risk profiles. Female MSH6 mutation carriers have a lower CRC risk and a higher risk for developing endometrial carcinoma. As a consequence, surveillance colonoscopy starting at age 30 years instead of 20-25 years is more suitable. Also, prophylactic hysterectomy may be more indicated in female MSH6 mutation carriers compared to MLH1 and MSH2 mutation carriers.
林奇综合征（LS）与结直肠癌（CRC）及结外恶性肿瘤（如子宫内膜癌（EC））的高风险相关。风险取决于受影响的错配修复基因。本研究的目的是计算已证实的MLH1、MSH2和MSH6突变携带者中与LS相关癌症的累积风险。
研究人群包括67个已证实的LS家族。收集了包括突变状态和肿瘤诊断在内的临床信息。使用Kaplan-Meier生存分析计算并比较累积风险。
MSH6突变携带者，无论男性还是女性，在70岁时患CRC的风险最低，分别为54%和30%，男性发病年龄延迟3至5年。关于子宫内膜癌，女性MSH6突变携带者在70岁时的风险最高（61%），相比之下，MLH1突变携带者为25%，MSH2突变携带者为49%。此外，与MLH1和MSH2相比，EC发病年龄延迟5至10年。
尽管与LS相关癌症的累积终生风险相似，但MLH1、MSH2和MSH6突变似乎导致不同的癌症风险特征。女性MSH6突变携带者患CRC的风险较低，患子宫内膜癌的风险较高。因此，从30岁而非20至25岁开始进行监测性结肠镜检查更为合适。此外，与MLH1和MSH2突变携带者相比，女性MSH6突变携带者可能更适合进行预防性子宫切除术。
