SUN-829 The Association Between Genotypes Of Increased And Decreased Type 2 5α-reductase Activity And The Risk Of Early-onset Prostate Cancer.

Abstract Disclosure: T. Shkeleva: None. S. Kalinchenko: None. A. Tsybulsky: None. N. Igor: None. A. Andreeva: None. The Association Between Genotypes of Increased and Decreased Type 2 5α-Reductase Activity and the Risk of Early-Onset Prostate CancerIntroduction. There is conflicting evidence regarding the significance of genetic variants in SRD5A2 (type 2 5α-reductase) for the risk of prostate cancer. These genetic markers alter the efficiency of dihydrotestosterone synthesis from testosterone, affecting not only prostate function but also male health and aging. However, the influence of SRD5A2 genotype combinations on prostate cancer risk remains understudied, and research rarely accounts for the age of disease onset. Objective: This study aimed to investigate the association between SRD5A2 (steroid-5α-reductase type 2 enzyme) genotypes—linked to increased or decreased activity—and the risk of prostate cancer in patients under 55 years of age. Patients and Methods. This case-control study included 90 participants from Russia: 45 patients diagnosed with prostate cancer before age 55 and 45 healthy men aged 55-70 without prostate cancer. Participants completed questionnaires based on the American Society of Clinical Oncology (ASCO) criteria to exclude hereditary prostate cancer cases. Genotyping was performed for two SRD5A2 variants: V89L (rs523349)—associated with reduced enzyme activity. A49T (rs9282858)—associated with increased enzyme activity. Genotyping was conducted using the Allele company’s pyrosequencing system. Genotype/allele frequencies and haplotype analysis were determined using the SNPator web tool. Additional statistical comparisons of clinical data and SNPs were performed using PASW Statistics 15. Results: The SRD5A2 V89L (rs523349) variant (reduced enzyme activity) was associated with a higher risk of prostate cancer in patients under 55 (OR = 1.58, 95% CI: 0.77-3.64) under a dominant inheritance model (GG vs. GC+CC). The minor allele C (reduced activity) was more frequent in the prostate cancer group (49%) compared to NCBI European population data (35%). The SRD5A2 A49T (rs9282858) variant (increased activity) was more prevalent in the control group, but due to low allele frequency, this association was not statistically significant. Haplotype analysis revealed that participants with low-activity SRD5A2 haplotypes (GGCC+GGGC) had higher odds of early-onset prostate cancer (OR = 1.44, 95% CI: 0.62-3.33) compared to normal/high-activity haplotypes. Conclusions: SRD5A2 genotypes associated with normal or increased type 2 5α-reductase activity—and their combinations—were not linked to a higher risk of prostate cancer in patients under 55 years old. Presentation: Sunday, July 13, 2025