title: Genetic mutation risk calculation in Lynch syndrome inheritance: Evaluating the utility of the PREMM1,2,6model in Lyon: The first French study.
abstract: Lynch syndrome is due to germline mutations in mismatch repair genes: MLH1, MSH2, MSH6 and PMS2. It is characterized by an increased risk of various cancers including colorectal and endometrial cancers. Early diagnosis of these patients allows for appropriate surveillance and improves survival rates. Differentiating between patients who should undergo genetic testing and those for whom it is not necessary is difficult despite various established criteria (Amsterdam and Bethesda). Often, health professionals meet in multidisciplinary committees (MDC) to discuss patient cases regarding Lynch syndrome. In this study, we evaluated if the prediction model PREMM1,2,6could be used to enhance MDC decision-making and whether it should be included in our own routine practice and in those of other French teams. Using the prediction model in our cohort would have avoided 12% of the analyses recommended by our MDC. Furthermore, all patients with a mutation in one of the MMR genes would have been detected. In addition, according to the model, we should have provided 20% more genetic testing, which suggests that the decision-making criteria used by the professionals in our MDC, was too restrictive. These results suggest that PREMM1,2,6should be used in current practice to validate the decisions of the MDC before genetic testing is performed in complex cases. The model should be added as a major quality criterion for genetic testing, along with somatic tests, as previously reported in the literature.
authors.affiliation: Hôpital Édouard-Herriot, 5, place d'Arsonval, 69003 Lyon, France; Centre hospitalier Lyon Sud, 165, chemin du Grand-Revoyet, 69310 Pierre-Bénite, France; French association of genetic counselors, 16, rue de Lorraine, 13008 Marseille, France. Electronic address: Souria.aissaoui@chu-lyon.fr.
authors.forename: Souria
authors.initials: S
authors.lastname: Aissaoui
authors.affiliation: French association of genetic counselors, 16, rue de Lorraine, 13008 Marseille, France; Centre hospitalier métropole Savoie, place Lucien-Biset, 73000 Chambéry, France.
authors.forename: Charline
authors.initials: C
authors.lastname: Cartellier
authors.affiliation: Hôpital Édouard-Herriot, 5, place d'Arsonval, 69003 Lyon, France; French association of genetic counselors, 16, rue de Lorraine, 13008 Marseille, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Seytier
authors.affiliation: Hôpital Édouard-Herriot, 5, place d'Arsonval, 69003 Lyon, France; Centre hospitalier Lyon Sud, 165, chemin du Grand-Revoyet, 69310 Pierre-Bénite, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Giraud
authors.affiliation: Hôpital Édouard-Herriot, 5, place d'Arsonval, 69003 Lyon, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Calender
mesh_terms: D026683:Advisory Committees / Q000458:organization & administration*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000235:genetics*; D053843:DNA Mismatch Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D003657:Decision Making; D055088:Early Detection of Cancer / Q000379:methods; D005190:Family; D005260:Female; D005602:France; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2 / Q000235:genetics; D000070957:MutL Protein Homolog 1 / Q000235:genetics; D051718:MutS Homolog 2 Protein / Q000235:genetics; D011237:Predictive Value of Tests; D018570:Risk Assessment / Q000379:methods
chemical_list: D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein
keywords: Familial cancer management; Genetic diagnosis; Lynch syndrome; Multidisciplinary decision-making; Risk assessment