Risk of Cancer in Cases of Suspected Lynch Syndrome Without Germline Mutation

Autor: Juan Clofent, Miriam Juárez, Alejandro Brea–Fernández, Joaquín Cubiella, Clara Ruiz–Ponte, Víctor Manuel Barberá, José Carlos Marín Gabriel, Angel Carracedo, Luísa Castro, Angel Lanas, Josep Maria Reñe, Sergi Castellví–Bel, Lucía Pérez–Carbonell, Montserrat Andreu, María Rodríguez Soler, David Nicolás Pérez, Artemio Payá, Adela Castillejo, Xavier Llor, Rosa M. Xicola, Antoni Castells, Cristina Alenda, Francesc Balaguer, Rodrigo Jover, Luis Bujanda, José Luis Soto, Pedro Zapater, Carla Guarinos, Xavier Bessa
Přispěvatelé: Biotecnología, Universidad de Alicante. Departamento de Biotecnología
Rok vydání: 2013
Předmět:
Oncology
Male
Pathology
Genetic testing
DNA Repair
DNA Mismatch Repair
Cancer risk
Risk Factors
PMS2
Aged
80 and over
education.field_of_study
Incidence
Gastroenterology
Nuclear Proteins
DNA
Neoplasm
Middle Aged
Immunohistochemistry
Lynch syndrome
Population Surveillance
Female
Microsatellite Instability
MutL Protein Homolog 1
Adult
medicine.medical_specialty
congenital
hereditary
and neonatal diseases and abnormalities
Population
Biología Celular
MLH1
Article
Inherited colon cancer
Germline mutation
Internal medicine
medicine
Humans
education
neoplasms
Germ-Line Mutation
Adaptor Proteins
Signal Transducing
Aged
Hepatology
business.industry
Microsatellite instability
Cancer
nutritional and metabolic diseases
medicine.disease
Colorectal Neoplasms
Hereditary Nonpolyposis
digestive system diseases
MSH2
Spain
business
Zdroj: RUNA. Repositorio da Consellería de Sanidade e Sergas
Servizo Galego de Saúde (SERGAS)
GASTROENTEROLOGY
r-FISABIO: Repositorio Institucional de Producción Científica
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
RUA. Repositorio Institucional de la Universidad de Alicante
Universidad de Alicante (UA)
r-FISABIO. Repositorio Institucional de Producción Científica
instname
ISSN: 0016-5085
Popis: Background & Aims: Colorectal cancers (CRCs) with microsatellite instability (MSI) and a mismatch repair (MMR) immunohistochemical deficit without hypermethylation of the MLH1 promoter are likely to be caused by Lynch syndrome. Some patients with these cancers have not been found to have pathogenic germline mutations and are considered to have Lynch-like syndrome (LLS). The aim of this study was to determine the risk of cancer in families of patients with LLS. Methods: We studied a population-based cohort of 1705 consecutive patients, performing MSI tests and immunohistochemical analyses of MMR proteins. Patients were diagnosed with Lynch syndrome when they were found to have pathogenic germline mutations. Patients with MSI and loss of MSH2 and/or MSH6 expression, isolated loss of PMS2 or loss of MLH1 without MLH1 promoter hypermethylation, and no pathogenic mutation were considered to have LLS. The clinical characteristics of patients and the age- and sex-adjusted standardized incidence ratios (SIRs) of cancer in families were compared between groups. Results: The incidence of CRC was significantly lower in families of patients with LLS than in families with confirmed cases of Lynch syndrome (SIR for Lynch syndrome, 6.04; 95% confidence interval [CI], 3.58–9.54; SIR for LLS, 2.12; 95% CI, 1.16–3.56; P < .001). However, the incidence of CRC was higher in families of patients with LLS than in families with sporadic CRC (SIR for sporadic CRC, 0.48; 95% CI, 0.27–0.79; P < .001). Conclusions: The risk of cancer in families with LLS is lower that of families with Lynch syndrome but higher than that of families with sporadic CRC. These results confirm the need for special screening and surveillance strategies for these patients and their relatives. This work was supported by grants from Instituto de Salud Carlos III (PI-080726, INT-09/208, and PI11/026030), the Fondo de Investigación Sanitaria/FEDER (PS09/02368, 10/00384, 10/00918, 11/00219, and 11/00681), Fundació Olga Torres (CRP) and FP7 CHIBCHA Consortium (SCB and ACar), the Ministerio de Economía y Competitividad (SAF2010-19273), and Agència de Gestió d’Ajuts Universitaris i de Recerca (2009 SGR 849). SCB is supported by a contract from the Fondo de Investigación Sanitaria (CP03-0070). CIBERER and CIBERehd are funded by the Instituto de Salud Carlos III.
Databáze: OpenAIRE
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