Genetic and Non-Genetic Risk Factors in Prostate Cancer: Towards a Precision Medicine Approach.

Prostate cancer (PCa) represents the most common malignancy among men in many countries, including the Czech Republic. While most cases are sporadic, approximately 10 % are attributed to hereditary factors, particularly germline pathogenic variants in genes such as BRCA1 and BRCA2, ATM, and CHEK2. These variants are associated with higher disease susceptibility, aggressive tumour behaviour and earlier onset of the disease. In parallel, modifiable and non-modifiable risk factors - including age, ethnicity, lifestyle, obesity, exposure to environmental carcinogens - also play an important role in the development and progression of PCa. This review summarizes the current state of knowledge on both genetic and non-genetic risk factors for PCa and emphasizes their relevance for clinical risk stratification, early detection strategies and prevention. The paper also provides an overview of the implications of hereditary PCa in the context of targeted therapy, particularly PARP inhibitors and immunotherapy, and discusses how somatic tumour profiling may refine the therapeutic decision-making. By integrating epidemiological data, molecular diagnostic and recent clinical advances, this review enhances understanding of the genetic underpinnings of PCa and advocates for a comprehensive, precision medicine approach in PCa management. The review emphasizes the importance of early identification of high-risk individuals through germline genetic testing and polygenic risk assessment, which can guide screening and personalized treatment and ultimately improve patient outcomes.