Abstract
Abstract In Europe, bladder cancer (BC) is the sixth most commonly diagnosed tumor and the second most common cause of death among patients with genitourinary tract malignancies. The ability to repair DNA damage is strongly associated with the risk of cancer and inter-individual variation in DNA repair capacity (DRC) might account for different susceptibility of developing cancer. DRC represents a complex marker comprising the sum of several factors such as gene variants, gene expression, stability of gene products, and effect of inhibitors/stimulators. Individuals with low DRC will tend to accumulate more damage than those who have a better ability to repair such damage. This variability is modulated by the genetic background to which SNPs/haplotype combinations in DNA repair genes, as well as epigenetic regulation are likely to contribute. Phenotypic assays to evaluate DNA repair activity (in particular NER comet assay, H2AX phosphorylation and micronucleus assay) were performed on cryopreserved lymphocytes from 159 cases (collected before treatment) and 159 controls matched by age and smoking habits, enrolled in Turin Bladder Cancer Study (TBCS). We aimed at studying the relationship between DRC (evaluated by comet assay, micronuclei and H2AX phosphorylation assay) and bladder cancer integrating, gene expression and epigenetic profile data (methylation levels and microRNA expression). In particular, we performed an integrated analysis on the genotype/phenotype correlation in a population of bladder cancer cases and controls provided with detailed description of the follow-up for response to therapy/recurrence/survival. This integrated approach will help in elucidating the role of DRC (and its determinants) as predictive and prognostic marker and to identify combined biomarkers to be measured in blood cells as non-invasive predictive method. Citation Format: Barbara Pardini, Alessandra Allione, Simonetta Guarrera, Valentina Turinetto, Giovanni Fiorito, Fabio Rosa, Alessia Russo, Federica Modica, Claudia Giachino, Paolo Vineis, Carlotta Sacerdote, Giuseppe Matullo. DNA repair capacity, gene expression and epigenomic profiles in bladder cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5367. doi:10.1158/1538-7445.AM2014-5367
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