Table 1 Overview of recent predictive models for mismatch repair (MMR) gene mutation detection in Lynch syndrome
ModelPopulationOutcomeNeoplasms includedMethodPredictors in development cohorts
Barnetson et al22870 population based colorectal cancer patients <55 yearsPoint mutations at MLH1, MSH2, MSH6 and large rearrangements at MLH1, MSH2Colon and endometrialTwo stage model:1. Multivariate logistic regression analysis2. Refinement of carrier prediction’s performance with MSI and IHC dataProband: age, gender, tumour’s location, multiple tumoursFamily: CRC age <50 or ⩾50 years, presence of endometrial cancer in 1st degree relativesAUC = 0.82, 95% CI 0.72 to 0.91
PREMM1,2151914 individuals undergoing genetic testing for clinical suspicion of Lynch syndromePoint mutations and large rearrangements at MLH1, MSH2Colon, endometrial, other Lynch associated tumours, colonic adenomasMultivariate logistic regression analysis based on personal and family history (affected 1st and 2nd degree relatives)Proband: number of CRC, adenomas, endometrial cancer, other Lynch associated tumours, age at diagnosis of CRC, adenomas, endometrial cancerFamily: CRC, endometrial cancer, other Lynch associated tumours, age at diagnosis for CRC and endometrial cancer in 1st and 2nd degree relativesAUC = 0.80, 95% CI 0.77 to 0.83
MMRpro23Validation on 279 individuals from 226 clinic based familiesPoint mutations and large rearrangements at MLH1, MSH2, MSH6Colon and endometrialMendelian and Bayesian analysis incorporating the penetrance and prevalence of mutations and predictive values of MSI and IHC. Accounts for family size and unaffected individualsInput (proband and each 1st and 2nd degree relative):Relation to the proband, CRC and endometrial cancer status, age at diagnosis, current age or age at last follow-up if unaffected, MSI or IHC result, germline testing result of MLH1, MSH2 or MSH6AUC = 0.83, 95% CI 0.78 to 0.88
  • AUC, area under the receiver operating characteristic curve; CI, confidence interval; CRC, colorectal cancer; IHC, immunohistochemistry; MSI, microsatellite instability.