KLK3 and steroid 5-alpha reductase type II (SRD5A2) gene polymorphisms might affect clinical reliability of serum PSA measurement.

Background. Serum levels of fPSA, tPSA and of their ratio are used for prostate cancer (PC) screening. PSA synthesis depends on pathology, but also on KLK3 gene polymorphisms and on androgen transcriptional effects. The V89 isoform of Steroid 5-α reductase type II (SRD5A2) by enhancing diihydrotestosterone, might also enhance PSA. Methods. we ascertained whether -5429T>G, -5412T>C, -4643A>G KLK3 SNPs and their haplotypes, and V89L polymorphisms of SRD5A2 gene might affect the serum levels of fPSA, tPSA and f/tPSA. We studied 711 men consecutively subjected to prostate biopsy: 291 PC, 351 benign prostatic hyperplasia (BPH), 69 controls. Results. six KLK3 haplotypes were derived by Arlequin software; nine genotypes were inferred, with an overall frequency of: TTA/ TTA (62,03%), GCG/TTA (28.56%), GCA/TTA (3.37%), GCG/GCG (2.95%), TTA/TTG (1.55%), GCA/GCG (0.56%), GCG/TTG (0.42%), GTA/TTA (0.42%), TCA/TTA (0.14%). Among BPH patients, not PC or controls, fPSA (p=0.08) and tPSA (p<0.05) were decreased in TTA/TTA with respect to GCG/GCG and GCG/TTA (chi-square for trend: p=0.02 and p=0.01). Among PC, not BPH or controls, fPSA (p=0.03) and tPSA (p=0.01) were increased in SRD5A2 V/V homozygotes (chi-square for trend: p=0.01 and p=0.005). The NPV of tPSA <2.5 ug/L was higher (85%) among TTA/TTA than among GCG/TTA (67%). The PPV of tPSA >2.5 <= 10 ug/L and f/tPSA <=10% was higher among GCG/TTA (75%) than among TTA/TTA (64%). Conclusions. when evaluating serum fPSA and tPSA to obtain a differential diagnosis between PC and BPH, individual genetic background might affect serum levels and reduce diagnostic reliability of the test result.