| Abstract [eng] |
Prostate cancer (PCa) is the second most common cancer in men. Genetic mutation analysis allows the identification of specific genetic changes that predict the clinical course of PCa. The changes can be analysed using body liquids such as blood plasma, urine, or other fluids. This test, also known as a liquid biopsy, is minimally invasive and patient-friendly. The aim of the thesis – to evaluate the mutation prevalence in DNA damage response (DDR) pathway genes (ATM, BRCA1, BRCA2, CHEK2, and NBN) in blood and/or urine samples and to assess the impact of these mutations on the clinical course of PCa in the advanced and localized setting. DDR pathway gene mutations were prospectively evaluated in leukocyte and urine DNA from the advanced PCa group (n = 149) and leukocyte DNA from the localized PCa group (n = 139). Analysing leukocytes from patients with advanced and localized PCa, a high rate of mutations in DDR pathway genes (ATM, BRCA1, BRCA2, CHEK2) was found – 14.8% and 16.8%, respectively, and analysing urine samples from patients with advanced PCa – a 16.6% mutation rate was found for ATM, BRCA1, BRCA2, CHEK2, and NBN. With mutations in the DDR pathway genes, an aggressive disease course was observed in the advanced PCa group, with significant differences (in terms of poorer response to treatment and survival rates) compared to patients without mutations in these genes. Although no statistically significant differences were found, the study shows that the risk of localized PCa is three times higher in patients with mutations than in mutation-negative patients, and the disease is more aggressive according to clinical, radiological, and histopathological data. |
