Cancer Genetics and Epigenetics 2024, Vol.12, No.2, 97-105 http://medscipublisher.com/index.php/cge 100 4 Key Genetic Markers in Prostate Cancer Screening 4.1 BRCA1 and BRCA2 BRCA1 and BRCA2 are well-established genetic markers associated with an increased risk of prostate cancer (PCa). Mutations in these genes are linked to a higher incidence of aggressive and early-onset PCa. Studies have shown that BRCA2 mutation carriers have a significantly higher risk of developing prostate cancer compared to non-carriers, with a higher likelihood of poor prognosis and reduced overall survival (Cui et al., 2017; Brönimann et al., 2020). BRCA1 mutations, while less common, also contribute to increased PCa risk and are associated with more aggressive disease phenotypes (Na et al., 2017). The detection of BRCA1/2 mutations is crucial for identifying individuals at high risk and can inform targeted screening and therapeutic strategies, such as the use of PARP inhibitors in BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC) (Figure 2) (Tukachinsky et al., 2021; Chi et al., 2023). Figure 2 491 patient matched samples (Adopted from Chi et al., 2023) Chi et al. (2023) demonstrated a high concordance between tumor tissues and circulating tumor DNA (ctDNA) in a study involving 491 patient samples, particularly in terms of the presence or absence of BRCA1, BRCA2, and ATM genes. ctDNA serves as a valuable complement in identifying patients with metastatic castration-resistant prostate cancer (mCRPC) harboring BRCA or ATM gene mutations, especially in cases where there is insufficient or no tissue available for genetic analysis. The detection of BRCA1/2 mutations not only helps in identifying high-risk individuals but also guides the targeted treatment strategies using PARP inhibitors. The application of PARP inhibitors in patients with BRCA-mutated mCRPC has shown potential in personalized treatment, offering new therapeutic options and hope for these patients. 4.2HOXB13 HOXB13 is another significant genetic marker in prostate cancer screening. Mutations in the HOXB13 gene, particularly the G84E variant, have been associated with an increased risk of hereditary prostate cancer. This gene plays a role in prostate development and function, and its mutations are linked to early-onset and familial forms of the disease (Dias et al., 2018). The Philadelphia Prostate Cancer Consensus Conference 2017 highlighted the importance of testing for HOXB13 mutations in individuals with a family history of prostate cancer to better stratify risk and guide screening protocols. 4.3 Other significant markers In addition to BRCA1/2 and HOXB13, other genetic markers such as CHEK2 and ATM have been identified as significant in prostate cancer screening. CHEK2 mutations, although less prevalent, are associated with moderate increases in prostate cancer risk and can contribute to familial cancer syndromes (Zhen et al., 2018; Woodward et al., 2024). ATM mutations are particularly noteworthy as they are linked to both increased risk and aggressive disease phenotypes. Studies have shown that ATM mutations are associated with grade reclassification in men
RkJQdWJsaXNoZXIy MjQ4ODYzNQ==