Age-Dependent Cancer Risk Is not Different in betweenMSH2andMLH1Mutation Carriers

[摘要] Lynch syndrome is mostly characterized by early-onset colorectal and endometrial adenocarcinomas. Over 90% of the causal mutations occur in two mismatch repair genes,MSH2andMLH1. The aim of this study was to evaluate the age-dependent cancer risk inMSH2orMLH1mutation 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 forMSH2andMLH1mutation 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.

[学科分类] 流行病学