Accession Number:

ADA411444

Title:

Base Excision Repair Gene Mutations and Polymorphisms as a Potential Modifier of Breast Cancer Risk

Descriptive Note:

Final rept. 15 Sep 2001-14 Sep 2002

Corporate Author:

INSTITUTE FOR CANCER RESEARCH PHILADELPHIA PA

Personal Author(s):

Report Date:

2002-10-01

Pagination or Media Count:

11.0

Abstract:

Our hypothesis is that 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 MEDlMBD4, both DNA N-glycosylases that remove the T residue in a TU mismatch and the U residue in a UU mismatch. Our analysis revealed that neither MED1 nor TDG polymorphisms appear to be related to breast cancer of the general population. Curiously, compounded heterozygous exon 5 and exon 10 polymorphisms of the TDG gene, in our analysis of 590 patients is under-represented. 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 latter can be a checkpoint for eliminating defective gene coding for defective enzymes that may be damaging later in life. We observed that the exon 10 polymorphism of TDG is unusually high in frequency in the high risk ovarian population. This potentially important finding needs further examination with a larger population in the future.

Subject Categories:

  • Genetic Engineering and Molecular Biology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE