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: P Manders, L Spruijt, C M Kets, H W Willems, D Bodmer, K M Hebeda, I D Nagtegaal, J H J M van Krieken, M J L Ligtenberg, N Hoogerbrugge
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 47 Issue 9 Pg. 1407-13 (Jun 2011) ISSN: 1879-0852 [Electronic] England
• PMID: 21273057 (Publication Type: Journal Article)
• Copyright: Copyright © 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Adaptor Proteins, Signal Transducing
• MLH1 protein, human
• Nuclear Proteins
• MutL Protein Homolog 1

Topics

• Adaptor Proteins, Signal Transducing (genetics)
• Adult
• Age Factors
• Aged
• Cohort Studies
• Colorectal Neoplasms (diagnosis, genetics)
• Colorectal Neoplasms, Hereditary Nonpolyposis (diagnosis, genetics)
• DNA Methylation
• Family Health
• Female
• Germ-Line Mutation
• Humans
• Male
• Microsatellite Instability
• Middle Aged
• Models, Genetic
• MutL Protein Homolog 1
• Nuclear Proteins (genetics)
• Risk