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The genes involved in DNA repair system play a crucial role in the protection against mutations .It has been hypothesized that functional deficiencies in highly conserved DNA repair processes resulting from polymorphic variation may increase genetic susceptibility to breast cancer. There are multiple pathways to repair the different types of DNA damage and maintain genomic integrity among them is the nucleotide excision repair (NER) and the base excision repair (BER) pathways. Aim & methods: The aim of the present study was to examine the relation between the DNA repair gene polymorphisms and breast cancer (BC) risk in Egyptian females and to analyze their relation to clinico-pathological parameters of BC and also to investigate the synergistic effect of both genes on BC susceptibility . Both XPD and XRCC1 polymorphisms were characterized in 100 BC Egyptian females and 100 healthy women who had no history of any malignancy by amplification refractory mutation system -polymerase chain reaction (PCR) (ARMS) method and PCR with confronting two-pair primers(PCR–CTPP) , using DNA from peripheral blood in a case control study. RESULTS: our results revealed that the frequencies of AA genotype of XPD codon 312 polymorphism were significantly higher in the breast cancer study patients than in the normal individuals(p≤0.003), and did not observe any association between the XRCC1 Arg399Gln polymorphism and risk of developing breast cancer Also, no association between both XPD Asp312Asn and XRCC1 A399G polymorphisms and the clinical characteristics of disease Finally ,the combination of AA(XPD)+AG(XRCC1) were significantly associated with breast cancer risk. In conclusion, the present results suggest that, XPD gene is an important candidate gene for susceptibility to breast cancer. Also, gene–gene interaction between XPD(AA)+XRCC1(AG) polymorphism may be associated with increased risk of breast cancer in Egyptian women.

Impact of DNA Repair Gene Polymorphisms (XPD and XRCC1) on the Risk of Breast Cancer in Egyptian Female Patients