51 Background: Significant variation in response duration and overall survival exists among prostate cancer (PCa) patients treated with ADT. Germ-line SNPs affecting function of genes critical to hormone synthesis, transport, metabolism, binding sites, and degradation may contribute to variability in clinical outcomes observed in PCa patients treated with ADT.
METHODS
Between 1/07 and 10/08, all PCa patients seen in the Indiana University Simon Cancer Center oncology clinics were approached for recruitment to the Prostate Cancer Genetic Risk Evaluation of SNPs Study (PROGRESS). Participants completed a demographic and clinical questionnaire and provided a peripheral blood sample. Only patients with confirmed ADT initiation dates were included in this analysis. Germ-line DNA was analyzed for SNP genotyping on a 128-SNP chip using a TaqMan OpenArray GT Kit (Applied Biosystems). The chip included genes critical to hormone signaling, transport, and elimination pathways with minor allele frequencies > 5%. Patients were followed for progression-free survival (PFS) and overall survival (OS) endpoints. Univariable analyses were performed to identify significant associations between SNP genotype, clinical parameters, and PFS and OS outcomes.
RESULTS
107 patients with PCa initiated on ADT enrolled. Demographics included: age (median)-69 yrs, prostate specific antigen (PSA) (median)-28.0 ng/ml, PSA doubling time (median)-4.9 months, biochemical/metastatic-25%/75%, concurrent anti-androgen therapy-44%. No clinical parameters were associated with PFS and OS. Significant SNP associations with PFS and OS are summarized in the Table.
CONCLUSIONS
Interpatient differences in hormone pathway germ-line SNPs may contribute to variability in clinical outcomes in patients treated with ADT. [Table: see text] [Table: see text].