Base Excision Repair Gene Mutations and Polymorphisms as a Potential Modifier of Breast Cancer Risk
Abstract
Functional redundancy in Base Excision repair (BER) may permit polymorphism to accumulate in these parallel pathways. Deficiencies in BER may lead to elevated spontaneous mutation rates and an earlier onset of cancer. We have analysed two BER enzymes: TDG and MED1(MBD4), both DNA N-glycosylases that remove the T residue in a T/G mismatch and the U residue in a U/G mismatch. Our analysis of 100 cancer patients revealed only one common polymorphism and no rare polymorphisms for MED1. MED1 polymorphisms are random and appear not to be related to cancer. The TDG gene revealed two common polymorphisms, in exon 5 and exon 10, and no rare polymorphisms, in our analysis of 268 patients. Curiously, we observed no patient that harbors both polymorphisms when eight such patients were expected based on the allelic frequency of these polymorphisms. If this observation holds true for a larger population study, it may imply that the TDG gene has a second role in humans besides DNA repair, and that the presence of both alleles in a person may lead to embryonic lethality. The OGG1 gene and APE1 gene will be examined next to test for linkage to the polymorphisms in the TDG gene.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2001
- Accession Number
- ADA398986
Entities
People
- Anthony T. Yeung