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Medline ® Abstract for Reference 100

of '结直肠癌的分子遗传学'

Risk of cancer in cases of suspected lynch syndrome without germline mutation.
Rodríguez-Soler M, Pérez-Carbonell L, Guarinos C, Zapater P, Castillejo A, BarberáVM, Juárez M, Bessa X, Xicola RM, Clofent J, Bujanda L, Balaguer F, ReñéJM, de-Castro L, Marín-Gabriel JC, Lanas A, Cubiella J, Nicolás-Pérez D, Brea-Fernández A, Castellví-Bel S, Alenda C, Ruiz-Ponte C, Carracedo A, Castells A, Andreu M, Llor X, Soto JL, PayáA, Jover R
Gastroenterology. 2013 May;144(5):926-932.e1; quiz e13-4. Epub 2013 Jan 24.
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.
Unidad de Gastroenterología, Hospital General Universitario de Alicante, Alicante, Spain.