PROGNOSTIC MARKERS FOR PROSTATE CANCER RECURRENCE

摘要

Purpose. The relationship between inherited genetic variations in 5a-reductase type 1 (SRD5A1) and type 2 (SRD5A2) genes and the risk of biochemical recurrence after radical prostatectomy (RP) in prostate cancer (PCa) remains a fairly unexplored area of research. Patients and Methods. We studied 526 men with organ-confined and locally advanced PCa with a median follow-up time of 7.4 years. We investigated the effects of allelic variants of SRD5A1 and SRD5A2 genes and haplotype-tagging single nucleotide polymorphisms (htSNPs; n=19) on recurrence-free survival after RP using Kaplan-Meier plots, the log-rank test, and Cox proportional hazard models. Results. Upon adjusting for known prognostic clinical and pathological factors, eight htSNPs were shown to be independent predictors of recurrence. The SRD5A1 rs 166050 polymorphism was associated with an increased recurrence risk of HR=1.83 (95% CI, 1.04-3.21; P=0.035), while the rs518673 in SRD5A1 was associated with a decreased risk (HR=0.59, 95% CI, 0.41-0.85; P=0.004). The SRD5A2 gene was strongly associated with the risk of relapse with six polymorphisms being positively associated with recurrence including the known SRD5A2 V89L (rs523349) (HR=2.14, 95% CI, 1.23-3.70; P=0.007) and a protective htSNP rs12470143 with a HR of 0.66, (95% CI, 0.46-0.95; P=0.023). By combining SRD5A1 (rs518673T) and SRD5A2 (rs 12470143 A), the protective effect was shown to be additive with the maximum protection conferred by 3 or 4 alleles (HR=0.33, 95% CI, 0.17-0.63; P=0.001). Conclusion. Germline polymorphisms in 5a-reductase genes are independent prognostic genetic biomarkers that predict PCa biochemical recurrence after radical prostatectomy and may represent useful molecular tools for a genotype-tailored clinical approach.