Risk of cancer in cases of suspected lynch syndrome without germline mutation.
Gastroenterology
; 144(5): 926-932.e1; quiz e13-4, 2013 May.
Article
in En
| MEDLINE
| ID: mdl-23354017
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA, Neoplasm
/
Nuclear Proteins
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Colorectal Neoplasms, Hereditary Nonpolyposis
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Population Surveillance
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Adaptor Proteins, Signal Transducing
Type of study:
Clinical_trials
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Diagnostic_studies
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Etiology_studies
/
Incidence_studies
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Prognostic_studies
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Risk_factors_studies
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Screening_studies
Limits:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
/
Middle aged
Country/Region as subject:
Europa
Language:
En
Journal:
Gastroenterology
Year:
2013
Document type:
Article
Affiliation country:
Spain
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA