Estrogen receptors alpha (rs2234693 and rs9340799), and beta (rs4986938 and rs1256049) genes polymorphism in prostate cancer: evidence for association with risk and histopathological tumor characteristics in Iranian men.
We evaluated the effect of estrogen receptor (ER)-α and ER-β genes polymorphisms on development of prostate cancer (PCa) and its correlation with serum reproductive hormones and with clinicopathological characteristics in a sample of Iranian men. One hundred sixty-two men with PCa (mean age 63.7 ± 3.4 years) and 324 age-matched healthy controls (mean age 63.1 ± 3.2 years) were recruited in this study. Genotypes for ER-α and ER-β genes polymorphisms were identified by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Serum levels of reproductive hormones were also measured. Of PCa patients, 38.3%, and 61.7% had localized and advanced tumor, and 45.7%, and 54.3%, had low grade and high-grade cancer, respectively. There was a significant difference in genotype frequency distribution of ER-α gene polymorphism (P = 0.002), and ER-β gene polymorphism (P = 0.003) between cancer patients and controls. The ER-α Pvull C allele carriers (TC or CC) had a significantly increased risk of PCa compared with the TT homozygotes [odds ratio (OR) 3.12; 95% confidence interval (CI) 1.87-5.84, and OR = 4.73, 95% CI:2.44-7.33, respectively]. It was also found that the ER-α XbaI AG (OR = 4.36; 95% CI:2.47-6.68; P = 0.001) and ER-β AluI AG (OR = 2.66, 95% CI:1.61-4.16; P = 0.004) genotypes were significantly associated with increased risk of PCa. The ER-β RsaI genotype was not associated with PCa. Baseline serum free E2 levels tended to be lower in men with PCa (0.35 ± 0.04 pg/ml) compared to healthy men (0.48 ± 0.05 pg/ml). Genotypes which confer susceptibility for developing PCa, accompanied with lowest serum levels of free E2. In the Iranian population, genetic polymorphisms of the ER-α and ER-β genes may be involved in the etiology of PCa.
Clinical Center for Urological Disease Diagnosis and Private Clinic Specialized in Urological and Andrological Genetics, Tehran, Iran.
Mohammad Reza
MR
Safarinejad
Saba
S
Safarinejad
Nayyer
N
Shafiei
Shiva
S
Safarinejad
D000368:Aged; D016022:Case-Control Studies; D015257:DNA-Cytosine Methylases / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007492:Iran; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D011897:Random Allocation; D013739:Testosterone / Q000097:blood
C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D013739:Testosterone; C047084:DNA modification methylase PvuII; D015257:DNA-Cytosine Methylases