Results of our studies, performed on more than 700 subjects, have demonstrated that occupational or environmental exposures to genotoxic agents (i.e. benzene related compounds, pesticides, mercury ions, cigarettes smoke) were associated with elevated levels of cytogenetic damage and were followed by increased risks of cancers. Results have also shown that genotoxic exposures significantly reduced efficiency of DNA repair. Reported results suggested that deficiency in DNA repair could be related to genotoxic exposures and life-styles (diet, vitamins, smoking). Groups of unexposed or exposed to PAHs subjects from Prague, Kosice and Sofia were monitored under the EXPAH EC project in many health, biological and polymorphic features (i.e. CYP1A1, GSTM1, NAT2, EPHX4, XRCC1). In those studies, results from application of the DNA repair competence assay in vitro have shown variability between subjects in responses of lymphocytes to the challenging X-ray dose and in repair efficiencies of the induced DNA damage. Significant decreases of repair efficiencies were observed when the whole investigated group was stratified first according to various genotypes and then to both exposures to PAHs (from cigarettes smoking and occupational). Application of the stochastic approach based on the molecular theory of radiation biology demonstrated that DNA repair competence was dependent on both combined exposure to PAHs and genetic predisposition (polymorphism). Other studies have shown that significant reduction of cellular repair efficacy of the DNA damage was also observed in groups of cancer patients. On the other hand, results of our studies have also shown a strong association between decrease in DNA repair efficiency and increase of aberration frequencies. In a conclusion, our results display that exposure to genotoxic agents, can be hazardous via directly induced cytogenetic damage or via alteration of the DNA repair processes, and can result in increased health risk, particularly in cancer risk. In both pathways, molecular and cytogenetic, results follow the stochastic theory of molecular actions. Results also show that application of the challenging X-rays dose and DNA repair competence assay combined with the detection of damage by SCGE, might be used as the fast, reliable and phenotype related biomarker of individuals vulnerability to the health risk. In epidemiology or pre-clinical studies, it might indicate subjects with elevated risk of health hazard and could also predict the cellular susceptibility to various treatments (environmental, occupational, accidental or therapeutic).