Analysis of the oxidative damage repair genes @entity32058 , XXXX , and @entity20701 in @entity1 from mismatch repair proficient HNPCC families (MSS-HNPCC).

@entity1 @entity72934 @entity20701 @entity72933 @entity56535 @entity5 @entity535 @entity14 @entity32058 @entity72932 @entity9552
PURPOSE: Several studies have described molecular differences between microsatellite stable @entity14 (MSS-HNPCC) and microsatellite unstable @entity5 (MSI-HNPCC). These differences highlight the possibility that other instability forms could explain @entity5 susceptibility in this group of families. The base excision repair (BER) pathway is the major DNA repair pathway for oxidative DNA damage. A defect in this pathway can result in DNA transversion mutations and a subsequent increased @entity5 risk. Mutations in @entity20701 have been associated with increased @entity14 ( @entity14 ) risk while no association has been described for @entity9552 or @entity32058 . EXPERIMENTAL DESIGN: We performed mutational screening of the three genes involved in defense against oxidative DNA damage in a set of 42 MSS-HNPCC families. RESULTS: Eight rare variants and 5 frequent variants were found in MSS-HNPCC @entity1 . All variants were previously described by other authors except variant @entity56535 in @entity9552 . Segregation studies were done and in silico programs were used to estimate the level of @entity535 conservation, protein damage prediction, and possible splicing alterations. Variants @entity9552 @entity72932 ; @entity20701 @entity72933 were detected in Amsterdam I families and cosegregate with @entity5 . Analysis of @entity9552 @entity72932 transcripts showed an inactivation of the splicing donor of exon 1. CONCLUSIONS: Two rare variants ( @entity9552 @entity72932 ; @entity20701 @entity72933 ) and one common polymorphism ( @entity32058 @entity72934 ) were associated with @entity14 risk. We show that the BER pathway can play a significant role in a number of MSS-HNPCC @entity14 . More studies could be of interest in order to gain further understanding of yet unexplained @entity14 susceptibility cases.
