Molecular and genetic patterns of prostate cancer in young men

Background: prostate cancer (PC) is the second most prevalent malignancy among male patients. The oncogenesis of PC may be attributed to alterations in multiple regulatory systems, potentially related to the presence of various genetic polymorphisms. Aim: to study the expression and activity of a number of specific genes in patients with PC aged less than 55 years, whose gene products, according to the literature, are implicated in carcinogenesis. Materials and Methods: the study cohort included 45 male patients with PC aged 55 years or younger. All participants underwent molecular genetic analysis of buccal epithelial cells to identify polymorphisms associated with alterations in the expression, activity, or susceptibility of genes encoding several hormones, receptors, enzymes, and other proteins implicated in PC pathogenesis. The following target genes were investigated: AR, SHBG, SRD5A2, CYP19A1, ESR1α, ESR2β, COMT, PGR, FADS2, PPARG, CYP27B1, and VDR Results: normal susceptibility, activity, or expression was most frequently observed for the VDR (82.2%), PGR (71.1%), and PPARG (68.9%) genes. In contrast, normal susceptibility/activity/expression was less commonly detected for the COMT (28.9%), CYP19A1 (35.6%), and ESR1α (37.8%) genes. Decreased susceptibility/activity/expression was predominantly observed for CYP27B1 (100%), COMT (71.1%), and CYP19A1 (64.4%), and less commonly for VDR (17.8%), PGR (28.9%), and PPARG (31.1%). Increased susceptibility/activity/expression was more frequently detected for ESR1α (62.2%) and FADS2 (22.2%), and less frequently for ESR2β (2.2%). Intermediate susceptibility was observed only for ESR2β (2.2%) and FADS2 (44.4%). Normal CYP19A1 activity was more frequently found in patients with prostate-specific antigen (PSA) levels ≤8.6 ng/mL than in those with PSA ≥8.6 ng/mL: 50.0% and 21.7%, respectively (p=0.047). Patients with PSA levels ≥8.6 ng/mL were more likely to exhibit decreased CYP19A1 activity. Among patients with a Gleason score ≤6, normal ESR2β expression was detected in 71.4% of cases, whereas in patients with a Gleason score ≥7, normal ESR2β expression was found in 41.2% of cases (p=0.072). A similar trend was observed for the PPARG gene: normal activity was present in 78.6% and 52.9% of cases in these respective groups (p=0.072). Conclusion: PC is a multifactorial disease arising from dysregulation of the body's regulatory systems. In patients with PC, polymorphisms contribute to alterations in gene expression associated with varying degrees of activity of receptors, enzymes, and other proteins involved in oncogenesis KEYWORDS: prostate cancer, carcinogenesis, androgen receptors, gene polymorphisms. FOR CITATION: Volodina I.V., Pavlov A.Yu., Dzidzaria A.G., Tsibulskii A.D. Molecular and genetic patterns of prostate cancer in young men. Russian Medical Inquiry. 2025;9(4):214–222 (in Russ.). DOI: 10.32364/2587-6821-2025-9-4-5