The MMRpro model accurately predicted the probability of carrying a cancer-susceptibility gene mutation for the Lynch syndrome

摘要

The Lynch syndrome, the most common form of hereditary colorectalncancer, is caused by germline mutations in MMR genes MSH2, MLH1,nand MSH6. Persons who inherit these mutations are at increased risk forncolorectal and endometrial cancer. Identifying unaffected persons who arenat risk is an important preventive health care strategy.nChen and colleagues evaluated MMRpro, a new test designed to predictnthe probability of a person having a deleterious germline mutationnin the MSH2, MLH1, or MSH6 genes and to provide an estimate ofnfuture cancer risk in unaffected persons, including mutation carriers,nuntested persons, and those in whom no mutation is found. MMRpronuses an algorithm that applies the Bayes theorem, taking into accountnthe colorectal and endometrial cancer status, including the tumor MSInstatus, of the proband and first- and second-degree relatives. As shownnby Chen and colleagues, MMRpro provided improved discriminatorynability over the Bethesda guidelines and better performance than thenLeiden model.