Abstract 3420: Androgen receptor (CAG)n polymorphism: A genomic marker for prostate cancer prognosis independent of histopathological parameters

Abstract The androgen receptor (AR) serves as a pivotal transcription factor in prostate cancer (PCa) development. Its transcriptional activity is linked to the number of glutamines in the N-terminal domain. While current screening for PCa and prognostic biomarkers include serum prostate-specific antigen (PSA) levels and histopathological characteristics (specifically, ISUP grade and margin involvement), the heterogeneity of these tumors underscores the need for additional markers to enhance clinical management. Thus, this study aimed at characterizing an Argentinian PCa patient cohort based on the CAG polymorphism (CAG)n in AR and establish associations between genotypes and clinical-pathological characteristics to refine disease prognosis. We designed a hospital-based case-case study for PCa patients to determine the association between AR polymorphisms and PCa biochemical relapse after radical prostatectomy (RP). We retrospectively recruited 112 patients histologically diagnosed with PCa at the Hospital de Clínicas José de San Martín, Buenos Aires, Argentina. All patients underwent RP as their primary therapeutic strategy. All patients were, by definition, Hispanics, predominantly of Caucasian ancestry and, at a lesser extent, Amerindian or African. Written informed consent and institutional review board approval were acquired. Blood samples were collected post-RP for genomic DNA extraction using the CTAB method. (CAG)n in AR was genotyped by fluorescent PCR followed by capillary electrophoresis, and correlations between genotypes and clinical-pathological variables were analyzed using R. Results categorized patients into three subgroups based on the length of the CAG tandem repeat in AR: long (>23 repeats, n=29), medium (20-23 repeats, n=44), and short (<20 repeats, n=38). No associations were found between the length of the polymorphism and age of diagnosis, pre-RP PSA serum values, ISUP grade, and margin involvement. However, patients with family cancer history had a higher frequency of the intermediate-length allele (p=0.02). Moreover, among patients with pre-RP PSA <10 ng/ml and intermediate-length allele had 2.72-fold risk of biochemical recurrence (BCR) (HR=2.72, 95%CI=1.05-7.03, p=0.039). Furthermore, multivariable BCR analysis including the ISUP grade and margin involvement as co-variates showed that the (CAG)n in AR was independent of these histopathological parameters (HRadj=3.37, 95%IC=1.24-9.10, padj=0.017). Altogether, the AR polymorphism is associated with family history of cancer. Consequently, determining the number of CAG repetitions in AR through a blood sample could serve as an independent prognostic marker in patients with PSA <10 ng/ml prior to PR, independent of the histopathological features. Citation Format: Gastón Mario Pascual, Agustina Sabater, Juan Bizzotto, Rocio Seniuk, Pablo Sanchis, Carlos M. Roggero, Carlos Scorticati, Osvaldo Mazza, Elba Vazquez, Ayelen Toro, Geraldine Gueron, Javier Cotignola. Androgen receptor (CAG)n polymorphism: A genomic marker for prostate cancer prognosis independent of histopathological parameters [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3420.