Searching for in vitro biomarkers of susceptibility to prostate and cervical cancers by analysis of chromosomal instability, gamma-H2AX foci, polymorphisms in DNA repair genes and apoptosis

Introduction and objective. According to the cancer epidemiology databases, cancer is the second leading cause of death in developing countries. Moreover, the WHO predicts a continuing increase in the incidence of cancer, extending this trend well into the next several decades. Hence, it seems obvious that the prediction of cancer susceptibility and early diagnosis is an important goal for modern biomedical sciences. The aim of this study is to clarify the value of chromosomal damage, capacity for the repair of double-strand breaks (DSBs), polymorphisms in DNA repair genes, and apoptosis as prognostic markers for prostate and cervical cancer. Materials and methods. 30 prostate cancer patients and 30 cervical cancer patients were enrolled into the study. In addition, 30 healthy female donors and 30 healthy male donors served as controls. The following endpoints were investigated: frequency of micronuclei, gamma-H2AX fluorescence, XRCC1 194C>T, XRCC1 399G>A, XRCC3 IVS5–14 A>G, OGG1 326 Ser>Cys polymorphisms and apoptosis. Results. Among all tested factors, only the homozygous variant (Arg/Arg) in XRCC1 (399 Arg/Gln) was strongly associated with prostate cancer risk, and only a low apoptotic response was connected with cervical cancer risk. The presented study confirmed a positive association between the frequency of MN and increased prostate and cervical cancer risk. However, such a biomarker is not cancer specific. In addition, the information gained by analyzing the gamma-H2AX fluorescence, as well apoptosis, had no value for predicting the risk of prostate and cervical cancers. Conclusions. The final conclusion of the study is that cancer susceptibility is a complex phenotype not readily detectable in relatively small studies by functional assays or analysis of SNP in few, selected genes.