A comparison of models used to predict MLH1, MSH2 and MSH6 mutation carriers

Background: MMRpro, prediction of mutations in MLH1 and MLH2 (PREMM1,2) and MMRpredict are models which were developed to predict the probability that an individual carries a Lynch syndrome-causing mutation. Each model utilizes data from personal and family histories of cancer. To date, no studies have compared these models in a cancer genetics clinic. The purpose of this study was to determine each model's ability to predict the probability of carrying a Lynch syndrome-causing mutation in individuals with a family history of colorectal cancer and to determine their clinical applicability. Methods: We obtained family pedigrees from 81 individuals who presented for Lynch syndrome testing due to a personal and/or family history of cancer. Data from each pedigree were entered into the models and analyzed using SPSS. Results: We found that MMRpredict, PREMM1,2 and MMRpro showed similar performances with areas under the receiver-operating characteristic curve of 0.731, 0.765 and 0.732, respectively. MMRpro showed the least dispersion of mutation probability estimates with a P value of 0.205, compared with 0.034 for PREMM1,2 and 0.001 for MMRpredict. Conclusion: We found all three carried out well in a cancer genetics setting, with PREMM1,2 giving slightly better estimates. There were some significant discrepancies between the models in cases where the proband had endometrial cancer.