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

Abstract

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.

Significant Association of Catechol-O-Methyltransferase Val158Met Polymorphism with Bladder Cancer Instead of Prostate and Kidney Cancer

“…Among these eligible studies, 4 were about bladder cancer (28-31), 9 about prostate cancer (8,17,19,(32)(33)(34)(35)(36)(37) and 1 about renal cell cancer (16). Except for 1 study with a mixed population (35), 7 studies included subjects that were Caucasian (17, 28-31, 33, 34) and 6 included Asian subjects (8,16,19,32,36,37).…”

“…They also identified a significant association between the COMT gene and renal cell carcinoma (16). However, the conclusions were controversial (17). On the basis of recent studies on the functions of the COMT gene and the inconsistent results obtained so far, this meta-analysis was conducted to investigate the association between cancer susceptibility and COMT Val158Met in different genetic models.…”

Association of estrogen receptor α PvuII and XbaI polymorphisms with prostate cancer susceptibility and risk stratification: a meta-analysis from case-control studies

“…Years of publications ranged from 2001 to 2015. Genotype frequencies among controls were consistent with the HWE test, except for three studies 11,24,26. STREGA scores ranged from 29 to 36, which suggested that all of these studies were qualified to the quantitative synthesis.…”

“Catechol-O-methyltransferase gene Val158Met polymorphism and prostate cancersusceptibility”

“…In eleven included studies, the smallest case sample size was 34 (Pazarbasi et al, 2013) and largest sample size was 1034 (Cussenot et al, 2007). Total cases and controls were 3,381 and 3,276 respectively.…”

“…In total cases, genotype percentage of GG, AG and AA was 34.13%, 49.01% and 16.86% respectively (Table 1). These studies were performed in different countries-France (Cussenot et al, 2007), Iran (Omrani et al, 2009), Japan (Suzuki et al, 2003(Suzuki et al, ,2007Tanaka et al, 2006), Turkey (Pazarbasi et al, 2013), UK (Low et al, 2006), USA (Nock et al,2006;Brureau et al, 2016;Tang et al, 2017) Meta-analysis: (Table 2).…”