Abstract 23: Functional DNA repair tests and their perspectives in molecular epidemiology (experience with subjects exposed to carcinogens and in cancer patients).

Abstract

Abstract DNA repair is crucial in maintaining universal genomic stability and preserving cellular functions. Defects in the DNA repair increase vulnerability to endogenous and exogenous DNA-damaging agents, consequent accumulation of mutations in the genome leading to development of several disorders. Individuals with defective DNA repair are at severely increased risk of developing cancer and other diseases. A number of factors are hypothesized to influence individual DNA repair capacity. Measurement of DNA repair capacity, through functional assays, therefore, represents an integrated marker that incorporates the effects of epigenetic factors, genetic polymorphisms, gene expression, stability of gene product, effect of inhibitors/stimulators, environmental factors and lifestyle factors. Functional DNA repair assays reflect the capacity of an organism to cope with a chronic exposure to numerous environmental and dietary genotoxicants and may be used as predictive markers in cancer therapy. We, recently, developed functional assays to measure nucleotide excision (NER) and base excision (BER) repair capacities in human tissues. Our initial data showed that in healthy subjects, occupationally exposed to potential chemical carcinogens, BER capacity inversely correlated with the levels of DNA damage and showed an increase with increased exposure. In contrast, both BER and NER capacities were significantly lower and DNA damage higher in incident colorectal cancer patients than in matched healthy control subjects. In colorectal cancer patients, interestingly, the DNA repair capacity increased to the levels observed in healthy control subjects following the completion of chemotherapy. In our other study, BER and NER capacities were measured in blood cells, healthy mucosa and tumor tissues from 70 patients with sporadic CRC. Lymphocytes in contrast to tumor tissues exhibited highest levels of BER and NER capacities. The definition of genetic and phenotypic landscape of the disease is, thus, further extended by DNA repair functional characteristics, both on the surrogate (systemic) and target tumor (topical level) tissues. Additional studies on DNA repair efficiency to determine influence on onset of the disease and in the context of gene-environment interactions are warranted. Acknowledgement: CZ GA CR: GA P304/10/1286 and GA P304/12/1585 Citation Format: Pavel Vodicka, Jana Slyskova, Rudolf Stetina, Ludmila Vodickova, Alessio Naccarati, Rajiv Kumar, Kari Hemminki. Functional DNA repair tests and their perspectives in molecular epidemiology (experience with subjects exposed to carcinogens and in cancer patients). [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 23.