title: Young age and a positive family history of colorectal cancer are complementary selection criteria for the identification of Lynch syndrome.
abstract: Families at high risk for Lynch syndrome can effectively be recognised by microsatellite instability (MSI) testing. The aim of the present study is to compare the effectiveness of a MSI test for the identification of Lynch syndrome in patients selected by a pathologist mainly based on young age at diagnosis (MSI-testing-indicated-by-a-Pathologist; MIPA), with that of patients selected by a clinical geneticist mainly based on family history (MSI-testing-indicated-by-Family-History; MIFH). Patients with a Lynch syndrome associated tumour were selected using MIPA (n=362) or MIFH (n=887). Germline DNA mutation testing was performed in 171 out of 215 patients (80%) with a MSI positive tumour. MSI was tested positive in 20% of the MIPA-group group compared to 16% in the MIFH-group (P=0.291). In 91 of 171 patients with MSI positive tumours tested for germline mutations were identified as Lynch syndrome patients: 42% in the MIPA-group and 56% in the MIFH-group (P=0.066). Colorectal cancer (CRC) or endometrial cancer (EC) presenting at an age below 50 years would have led to the diagnosis of Lynch syndrome in 89% of these families (CRC below 50 years: 88% and EC below 50 years: 12%). Families detected by MIPA were characterised more often by extracolonic Lynch syndrome associated malignancies, especially EC (P<0.001). Our results indicate that recognition of Lynch syndrome by CRC or EC below 50 years is as effective as a positive family history. Families from patients selected by individual criteria more often harbour extracolonic Lynch syndrome associated malignancies.
authors.affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Manders
authors.forename: L
authors.initials: L
authors.lastname: Spruijt
authors.forename: C M
authors.initials: CM
authors.lastname: Kets
authors.forename: H W
authors.initials: HW
authors.lastname: Willems
authors.forename: D
authors.initials: D
authors.lastname: Bodmer
authors.forename: K M
authors.initials: KM
authors.lastname: Hebeda
authors.forename: I D
authors.initials: ID
authors.lastname: Nagtegaal
authors.forename: J H J M
authors.initials: JH
authors.lastname: van Krieken
authors.forename: M J L
authors.initials: MJ
authors.lastname: Ligtenberg
authors.forename: N
authors.initials: N
authors.lastname: Hoogerbrugge
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000367:Age Factors; D000368:Aged; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000235:genetics; D019175:DNA Methylation; D005192:Family Health; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D008957:Models, Genetic; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics; D012306:Risk
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1