Olschwang Sylviane, Yu Kai, Lasset Christine, Baert-Desurmont Stéphanie, Buisine Marie-Pierre, Wang Qing, Hutter Pierre, Rouleau Etienne, Caron Olivier, Bourdon Violaine, Thomas Gilles
Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 891, Centre de Recherches en Cancérologie de Marseille, 13009 Marseille, France.
J Cancer Epidemiol. 2009;2009:791754. doi: 10.1155/2009/791754. Epub 2009 Mar 8.
Lynch syndrome is mostly characterized by early-onset colorectal and endometrial adenocarcinomas. Over 90% of the causal mutations occur in two mismatch repair genes, MSH2 and MLH1. The aim of this study was to evaluate the age-dependent cancer risk in MSH2 or MLH1 mutation carriers from data of DNA diagnostic laboratories. To avoid overestimation, evaluation was based on the age-dependent proportion of mutation carriers in asymptomatic first-degree relatives of identified mutation carriers. Data from 859 such eligible relatives were collected from 8 centers; 387 were found to have inherited the mutation from their relatives. Age-dependent risks were calculated either using a nonparametric approach for four discrete age groups or assuming a modified Weibull distribution for the dependence of risk on age. Cancer risk was estimated starting at 28 (25-32 0.68 confidence interval) and to reach near 0.70 at 70 years. The risks were very similar for MSH2 and MLH1 mutation carriers. Although not statistically significant, the risk in males appeared to precede that for females by ten years. This difference needs to be investigated on a larger dataset. If confirmed, this would indicate that the onset of the colonoscopic surveillance may be different in male and female mutation carriers.
林奇综合征主要表现为早发性结直肠癌和子宫内膜腺癌。超过90%的致病突变发生在两个错配修复基因，即MSH2和MLH1中。本研究的目的是根据DNA诊断实验室的数据评估MSH2或MLH1突变携带者中与年龄相关的癌症风险。为避免高估，评估基于已识别突变携带者无症状一级亲属中突变携带者的年龄相关比例。从8个中心收集了859名此类符合条件亲属的数据；其中387人被发现从亲属那里遗传了该突变。使用非参数方法对四个离散年龄组计算年龄相关风险，或者假设风险对年龄的依赖性符合修正的威布尔分布。癌症风险估计从28岁（25 - 32岁，0.68置信区间）开始，到70岁时接近0.70。MSH2和MLH1突变携带者的风险非常相似。虽然无统计学意义，但男性的风险似乎比女性提前十年。这种差异需要在更大的数据集中进行研究。如果得到证实，这将表明男性和女性突变携带者的结肠镜监测起始时间可能不同。
