Polymorphisms in androgen metabolism genes AR, CYP1B1, CYP19, and SRD5A2and prostate cancer risk and aggressiveness in Bulgarian patients.

Background/aim: The aim of our study was to elucidate the role of polymorphisms in AR, CYP1B1, CYP19, and SRD5A2 genes for prostate cancer (PC) development in Bulgarian patients.

Materials And Methods: We genotyped 246 PC patients and 261 controls (155 with benign prostate hyperplasia and 107 healthy population controls) using direct sequencing, PCR-RFLP, SSCP, and fragment analysis.

Results: The allele and genotype frequencies of most of the studied variants did not differ significantly between cases and controls. Increased frequencies of the C/C genotype and C allele of rs1056837 in CYP1B1, and genotype 7/8 of the (TTTA)n repeat polymorphism in CYP19, were observed in patients in comparison with controls.The 8/9 and the 7/12 genotypes of (TTTA)n in CYP19 showed suggestive evidence for association with decreased prostate cancer risk and the risk for aggressive disease, respectively. The haplotype analysis revealed 2 CYP1B1 haplotypes associated with PC risk reduction.

Conclusion: Some CYP1B1 haplotypes and genotypes of the CYP19 (TTTA)n repeat appeared to be associated with disease risk or aggressiveness in Bulgarian PC patients. In contrast, the SRD5A2 polymorphisms (V89L and (TA)n repeat), the CAG repeat in AR, and the Arg264Cys variant in CYP19A1 are most likely not implicated in prostate carcinogenesis.