Germline variations in genes involved in androgen biosynthesis and metabolic pathways may predict response to abiraterone acetate (AA) in men with metastatic castration refractory prostate cancer (mCRPC), and serve as prognostic and predictive biomarkers to allow more individualized therapy.
832 single nucleotide polymorphisms (SNPs) from the Illumina OmniExpress genotyping platform within the boundaries of 61 candidate genes reported to be involved in the androgen metabolic pathway were investigated for association with time to treatment failure (TTF) in 68 Caucasian men with mCRPC undergoing treatment with AA. Cox-proportional hazard analysis was employed using Gleason score (GS), age, level of alkaline phosphatase, and PSA at treatment initiation as covariates and assessing each SNP under an allele-carriage genetic model in which carriage of one or more minor alleles contributes to increased risk. Subset analyses were employed to determine if metastasis site or prior treatment by ketoconazole or docetaxel interact with the SNPs investigated.
Six SNPs in SULT1E1 were associated with TTF on AA therapy after False Discovery Rate (FDR) correction for multiple testing (q < 0.05) while controlling for GS, age, level of alkaline phosphatase, and PSA at treatment initiation.
SNPs in SULT1E1 (estrogen sulfotransferase gene) were significantly associated with TTF on AA therapy, and may serve as predictive markers for treatment with AA.