Journal of Clinical & Experimental Pathology
Open Access

Abstract

Oxidative damage has been related with the pathogenesis of colorectal cancer (CRC). The base excision repair (BER) pathway is the major DNA repair pathway for oxidative DNA damage. Polymorphisms in BER might thus increase a risk of CRC. In this work, we evaluated associations between the repair efficiency of oxidative DNA lesions and single-nucleotide polymorphisms of BER genes: the 194Trp/Arg and the 399Arg/Gln XRCC1, the 326Ser/Cys OGG1 and the 324Gln/His MUTYH and CRC occurrence in a Polish population. These polymorphisms were genotyped in 182 CRC patients and 245 control subjects, using a PCR-RFLP method. The level of oxidative damage and DNA repair capacity in lymphocytes and CRC tissue samples was evaluated by comet assay using FPG and Nth glycosidases. The 326Ser/Cys OGG1 and the 324Gln/His as well as the 324His/His MUTYH genotypes were found to be associated with an increased CRC risk, while no association was found for the XRCC1 gene polymorphisms. It was also demonstrated that CRC patients have reduced capacity of oxidative damage repair in comparison to healthy controls. Moreover, the ecrease efficiency of DNA repair were correlated with the 399Gln/Gln XRCC1 and the 324His/His MUTYH genotypes occurrence in CRC patients. The results obtained in our study indicated an association of OGG1 and MUTYH genes polymorphisms involved in oxidative DNA lesions repair with the risk occurrence of colorectal cancer in Polish patients. It was also found that studied polymorphisms might affect DNA repair capacity suggesting their role in CRC pathogenesis.

Biography

Jacek Kabzinski has completed his Ph.D. from Medical University of Lodz, at the field of genetics. Now he works at Department of Clinical Chemistry and Biochemistry where his studies concentrate at genetic and molecular basis of cancer (mainly colorectal cancer). He is a member of a Polish Biochemical Society.