To search for possible markers of the colon cancer risk and progress of the disease the level of DNA damage, the capacity of DNA repair and the polymorphism of some DNA repair genes were studied in the cells obtained from healthy donors and colon cancer patients.Using the PCR-RFLP method polymorphisms of APE1Asp148Glu (G>A, exon 10), NBS1Gln185Glu (G>C, exon 5), XRCC1Arg399Gln (G>A, exon 10), XPDAsp312Asn (G>A, exon 10) and XPDLys751Gln (A>C, exon 23) were assessed in DNA obtained from blood of 140 patients and 98 healthy donors. The levels of oxidative damage in the DNA of blood, cancer and normal colon epithelial cells as well as of 8-oxoguaninie (8-oxoGua) and 8-oxo deoxyguanosine (8-oxodG) in urine were assessed as markers of oxidative stress. In the group of 50 cancer patients the capacity of DNA repair was measured in lymphocytes exposured to ionising radiation in vitro.

The analysis of the distributions of polymorphic genotypes showed the differences among healthy donors and cancer patient groups for polymorphisms of APE 1 and XPD genes and the distribution of XPD 312 polymorhic variant differed also in the patient groups with different cancer localizations. Different tumor localization did not coincide with the differences in DNA oxidative damage but the levels of 5-hydroxymethyluracil detected in urine of patients with rectal and sigmoidal tumor localizations were higher than in urine of patients with other tumor localizations. Hierarchic cluster analysis applied to the results of DNA repair study in irradiated lymphocytes of 50 patients showed the presence of two dominating subgroups that differed in the level of induced DNA breaks and repair efficiency during 180’ of incubation and showed differences in the distribution of XPD variant form.

Our results suggest that the genetic background, presence or absence of polymorphic variants of some DNA repair genes, can differently modulate the risk of cancer in different fragments of colon. The results also suggest that colon epithelial cells can differ in DNA repair mechanisms depending on localization.

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3. An involvement of mammalian MTH1 protein (8-oxo-dGTPase) in carcinogenesis and its potential utilization as a molecular marker of carcinogenesis and oxidative stress
4. Repair of oxidative DNA damage in human cancers
5. Analyses of lymphocyte radiosensitivity in vitro for identification of predictive biomarkers of early response to radiotherapy in head and neck cancer patients
6. Polymorphism of DNA repair genes as a cancer risk factor; comparison between head and neck squamous cell carcinoma and colon cancer
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