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

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
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DOI:
10.1002/mc.21870
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发表时间:
2012-10-01
影响因子:
4.6
通讯作者:
Safarinejad, Shiva
Safarinejad, Shiva
中科院分区:
医学2区
文献类型:
--
作者:
Safarinejad, Mohammad Reza;Safarinejad, Saba;Safarinejad, Shiva

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我们评估了伊朗男性样本中雌激素受体(ER)-a和ER-β基因多态性对前列腺癌(PCa)发展的影响及其与血清生殖激素和临床病理特征的相关性。本研究招募了162名前列腺癌患者(平均年龄63.7 ± 13.4岁)和324名年龄匹配的健康对照(平均年龄63.1 ± 13.2岁)。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析确定ER-α和ER-β基因多态性的基因型。还测量了生殖激素的血清水平。在PCa患者中,38.3%和61.7%的患者患有局限性和晚期肿瘤,45.7%和54.3%的患者分别患有低级别和高级别癌症。ER-α基因多态性的基因型频率分布与正常对照组相比差异有统计学意义(P = 0. 05)。ER β基因多态性(P = 0.002); 0.003)之间的差异。与TT纯合子相比,ER-α Pvull C等位基因携带者(TC或CC)患PCa的风险显著增加[比值比(OR)3.12; 95%置信区间(CI)1.87 - 5.84,OR = 1.87 - 5.84]。4.73,95%CI:2.447.33]。ER-α XbaI AG(OR?=?4.36; 95% CI:2.476.68; P =?0.001)和ER-β I AG(OR?=?2.66,95% CI:1.614.16; P =?0.004)基因型与PCa风险增加显著相关。ER β RsaI基因型与PCa无关。前列腺癌患者基线血清游离E2水平较低(0.35 ± 0.04?pg/ml)与健康男性(0.48+/-0.05?pg/ml)。基因型赋予发展PCa的易感性,伴随着最低的血清游离E2水平。在伊朗人群中,ER-α和ER-β基因的遗传多态性可能参与PCa的病因学。(c)2012 Wiley Periodicals,Inc.
We evaluated the effect of estrogen receptor (ER)-a and ER-beta 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+/-13.4 years) and 324 age-matched healthy controls (mean age 63.1+/-13.2 years) were recruited in this study. Genotypes for ER-a and ER-beta genes polymorphisms were identified by the polymerase chain reactionrestriction fragment length polymorphism (PCRRFLP) 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-a gene polymorphism (P?=?0.002), and ER-beta gene polymorphism (P?=?0.003) between cancer patients and controls. The ER-a 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) 1.875.84, and OR?=?4.73, 95% CI:2.447.33, respectively]. It was also found that the ER-a XbaI AG (OR?=?4.36; 95% CI:2.476.68; P?=?0.001) and ER-beta AluI AG (OR?=?2.66, 95% CI:1.614.16; P?=?0.004) genotypes were significantly associated with increased risk of PCa. The ER-beta 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-a and ER-beta genes may be involved in the etiology of PCa. (c) 2012 Wiley Periodicals, Inc.