Monika Gos 1, Małgorzata Sadowska 2, Paweł Wiechno 2, Tomasz Demkow 2, Przemysław Janik 1
- 1 Zakład Biologii Komórki, Centrum Onkologii - Instytut im. M. Skłodowskiej-Curie w Warszawie
2 Klinika Nowotworów Układu Moczowego, Centrum Onkologii - Instytut im. M. Skłodowskiej-Curie w Warszawie
- Introduction. Prostate cancer is a multifactorial disease and its development depends on environmental and genetic factors. Polymorphisms in genes encoding proteins involved in androgen metabolism and signaling may determine individual susceptibility to prostate cancer as well as clinical features of the disease.
- Objectives. The aim of our study was to determine whether polymorphisms in genes of dihydrotestosterone biosynthesis (/TAAAA/n in CYP11A1, +34T/C in CYP17, V89L and A49T in SRD5A2), degradation (D85Y in UGT2B15) and signaling (/CAG/n and /GGN/n in AR) influence prostate cancer risk in Polish population. Also the correlation between these polymorphisms and clinical features (clinical stage, histopathological grade, patients' age and PSA level at diagnosis) of the disease has been analyzed.
- Materials and methods. One hundred eighty two men with histologically confirmed prostate cancer and 217 healthy men, randomly chosen from population were included in the study. The DNA was extracted from collected blood samples and the polymorphisms analysis was performed with standard molecular biology methods (PCR-RFLP, GeneScan). For statistical analysis the logistic regression model was used.
- Results. Variants containing at least one 85Y allele in UGT2B15 gene and short variants (Ł19 CAG repeats) of AR gene were more common among prostate cancer patients than in control group (83% vs 73.3%, p=0.02 for UGT2B15 and 18.3% vs. 12%, p=0.08 for AR). Therefore these variants correlated with higher risk of prostate cancer development (OR=1.8 and 1.6 respectively). Moreover, the examined polymorphisms correlated with clinical stage of the disease. The +34CC genotype in CYP17 gene as well as long (>22 CAG repeats) AR alleles were more prevalent in patients with metastatic disease (30.4% and 52.2%, respectively) as compared to patients with organ confined disease (T1/T2, 10.2% and 30.5%, respectively) or locally advanced disease (T3/T4, 22.6% and 33.9%, respectively). The observed differences were statistically significant (p<0.05) and the odds ratio for metastatic disease was over 2.0. The same genetic variants correlated with higher (>25 ng/ml) PSA level at diagnosis (p<0.05 for AR gene). Combinations in CYP11A1 gene containing at least one /TAAAA/4 allele and 89LL variant in SRD5A2 gene were more common (93.3% and 17.8% respectively) in patients with poorly differentiated cancer (>6 according to Gleason scale) than in men with well differentiated tumor (82.4% and 5.4%, respectively). These variants may correlate with higher histological aggressiveness of prostate cancer (OR>2.0).
- Conclusions. The genetic background (polymorphisms in genes of androgen metabolism) seems to be important factor influencing prostate cancer risk. The examined polymorphisms also correlated with tumor clinical features like clinical stage or histological grade.