Mismatch repair gene defects contribute to the genetic basis of double primary XXXX of the colorectum and endometrium.

@entity1204 @entity1 @entity6756 @entity5 @entity4311 @entity14 @entity4310
@entity14 ( @entity14 ) is a dominantly @entity4310 caused by germline defects of mismatch repair (MMR) genes. @entity1204 is the most common extracolonic @entity5 in @entity14 and is the primary clinical manifestation of the syndrome in some families. The cumulative incidence of @entity1204 among @entity14 mutation carriers is high, estimated to be from 22 to 43%. We hypothesized that @entity1 with double primary @entity5 of the colorectum and endometrium are likely to be members of @entity14 families. In order to determine how frequently @entity14 manifests in the context of double primary @entity5 , we examined alterations of two MMR genes, @entity4311 and @entity6756 , in 40 unrelated @entity1 affected with double primary @entity5 . These cases were identified using hospital-based and population-based @entity5 registries in Ontario, Canada. MMR gene mutations were screened by single-strand conformation polymorphism analysis and confirmed by direct sequencing. Eighteen percent (seven of 40) were found to harbor mutations of one of the two MMR genes. Analysis of @entity14 of mutation-negative probands found microsatellite instability in seven of 20 cases. Six of seven mutation-positive probands had strong family histories suggestive of @entity14 . First degree relatives of mutation-positive probands had a very high relative risk (RR) of @entity14 (RR = 8.1, CI 3. 5-15.9) and @entity1204 (RR = 23.8, CI 6.4-61.0). The relative risk of mutation-negative cases was 2.8 (CI 1.7-4.5) for @entity14 and 5.4 (CI 2.0-11.7) for @entity1204 . We recommend that all double primary @entity1 with @entity5 at these sites should have a genetic evaluation, including molecular analysis for @entity14 where appropriate.
