Evaluation of the effects of androgen receptor gene trinucleotide repeats and prostate-specific antigen gene polymorphisms on prostate cancer

The number of trinucleotide repeats [CAG (coding for polyglutamine), GGC (coding for polyglycine)] in the first exon of the androgen receptor (AR) gene and prostate-specific antigen (PSA) gene androgen response element I A/G polymorphism are both related to prostate cancer prognosis. We investigated whether these genomic changes occur in the AR and PSA genes, which are usually found in individuals with prostate cancer, of Turkish patients and to find out their distribution in the population. We used PCR and PCR-RFLP assays for AR and PSA genes, respectively, to detect molecular changes in 44 prostate cancer patients. Our findings indicate that individuals with prostate cancer tend to have around 18 CAG trinucleotide repeats. We observed significant differences between 22 controls, 33 benign prostate hyperplasia (BPH) patients and 44 adenocarcinoma patients for long CAG repeats. However, we did not find any significant differences in GGC repeats between controls, BPH and adenocarcinoma patients (P = 0.408). We also did not observe significant differences in the PSA A/G polymorphism frequency between controls, BPH and adenocarcinoma patients (P = 0.483). In conclusion, CAG and GGC repeats in the AR and PSA gene polymorphisms may be associated with prostate cancer risk and BPH in the Turkish population.     

Genetic polymorphisms of estrogen receptor alpha and catechol-O-methyltransferase genes in Turkish patients with familial prostate carcinoma

OBJECTIVES:

Estrogen is one of the most crucial hormones participating in the proliferation and carcinogenesis of the prostate glands. Genetic polymorphisms in the estrogen metabolism pathway might be involved in the risk of prostate carcinoma development. We evaluated the association between genetic polymorphisms in estrogen receptor alpha (ESR1) and catechol-O-methyltransferase (COMT) genes and the risk of developing familial prostate carcinoma.

MATERIALS AND METHODS:

In this study, 34 cases with prostate carcinoma whose first-degree relatives had prostate carcinoma and 30 healthy age-matched male controls were enrolled. The genotypes of ESR1 and COMT genes were analyzed employing polymerase chain reaction-restriction fragment length polymorphism method. 34 cases with prostate carcinoma, whose first degree relatives had prostate carcinoma and 14 age-matched male controls were enrolled to analyze the genotype of these two genes.

RESULTS:

Among control patients, the ESR1 PvuII genotypes of C/C, C/T and T/T were observed in 37%, 26% and 37%, respectively, whereas the C/C, C/T and T/T genotypes were observed in 18%, 41% and 41% of case patients, respectively. Among controls, the ESR1 PvuII allele frequencies of C and T were equally observed, whereas the C and T allele frequencies were observed in 38% and 62% of patients, respectively. Among ESR1 PvuII genotypes there were not any significant difference in terms of genotype (P = 0.199) and allele (P = 0.181) frequencies. Among controls, the ESR1 XbaI genotypes of G/G, G/A and A/A were observed in 33%, 37% and 33%, respectively, whereas the G/G, G/A and A/A genotypes were observed in 12%, 47% and 41% of patients, respectively. Among controls, the ESR1 XbaI allele frequencies of A and G were observed equally, respectively, whereas the A and G frequencies were observed in 65% and 35% of patients, respectively. Among ESR1 Χ baI, there was not any significant difference in terms of genotype (P = 0.111) and allele (P = 0.093) frequencies. But the C/C genotype of the PvuII site and G/G genotype of the XbaI site in the ESR1 gene were associated significantly with the risk of developing prostate carcinoma. The G/G, G/A and A/A genotypes of the COMT gene were observed in 50%, 29% and 21% of control patients and in 53%, 21% and 26% of case patients, respectively. The A and G allele frequencies of the COMT gene were observed in 36.7%, 63.3% of control patients and in 36.8%, 63.2% of case patients, respectively. In COMT gene, there was not any significant difference in terms of genotype (P = 0.843) and allele (P = 0.991) frequencies. But the G/A genotype of the COMT gene had a weak tendency toward increased risk.

CONCLUSION:

Polymorphisms of ESR1 gene in the estrogen metabolism pathway were associated significantly with familial prostate carcinoma risk. Single nucleotide polymorphisms of low-penetrance genes are targets for understanding the genetic susceptibility of familial prostate carcinoma.