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细胞色素P450 1A1*2A基因多态性与克罗地亚人前列腺癌风险及侵袭性的关联研究

Association study of cytochrome P450 1A1*2A polymorphism with prostate cancer risk and aggressiveness in Croatians.

作者信息

Mandić Sanja, Horvat Vesna, Marczi Saska, Lukić Ivana, Galić Josip

出版信息

Coll Antropol. 2014 Mar;38(1):141-6.

Abstract

Cytochrome P450 1A1 (CYP1A1) is an enzyme participating in the bioactivation of various endogenous and environmental reactive compounds that can bind to DNA and thus induce cancerogenesis. Gene encoding the enzyme is expressed in the prostate tissue and is polymorphic. CYP1A1*2A gene polymorphism is associated with elevated enzyme activity and/or inducibility which can lead to accumulation of genotoxic compounds and consequently to cancerogenesis. We examined the association of this polymorphism with prostate cancer (PCa) risk and aggressiveness. The case-control study consisted of 120 PCa patients and 120 benign prostatic hyperplasia (BPH) controls, in Croatian population. Regarding aggressiveness, PCa patients were grouped according to the Gleason score (GS), tumor stage (T) and existence of distant metastasis (M). The polymorphism was analyzed using real-time polymerase chain reaction (PCR). We did not observe association of mutated allele with PCa risk, neither with PCa aggressiveness. Furthermore, frequency of polymorphic genotype was slightly higher in BPH group (16.6% vs. 14.2%, respectively) and also in less aggressive form of PCa (20.4% vs. 9.6% for GS < 7; 15.6% vs. 9.1% for T < 3; 16.7% vs. 10.0% for no distant metastasis). Comparing our findings with other published results, we can assume that the ethnicity influence the genotype distribution and thus may affect the etiology of PCa, even possibly in the way to cause an opposite effect among different ethnic groups. Given the small number of participants, results should be validated on the larger sample size.

摘要

细胞色素P450 1A1(CYP1A1)是一种参与多种内源性和环境反应性化合物生物活化的酶,这些化合物可与DNA结合,从而诱发癌症。编码该酶的基因在前列腺组织中表达且具有多态性。CYP1A1*2A基因多态性与酶活性升高和/或诱导性增加有关,这可能导致遗传毒性化合物的积累,进而引发癌症。我们研究了这种多态性与前列腺癌(PCa)风险及侵袭性之间的关联。这项病例对照研究纳入了克罗地亚人群中的120例PCa患者和120例良性前列腺增生(BPH)对照。关于侵袭性,PCa患者根据 Gleason评分(GS)、肿瘤分期(T)和远处转移(M)的存在情况进行分组。使用实时聚合酶链反应(PCR)分析多态性。我们未观察到突变等位基因与PCa风险以及PCa侵袭性之间存在关联。此外,多态基因型的频率在BPH组中略高(分别为16.6%对14.2%),在侵袭性较低的PCa形式中也较高(GS<7时为20.4%对9.6%;T<3时为15.6%对9.1%;无远处转移时为16.7%对10.0%)。将我们的研究结果与其他已发表的结果进行比较,我们可以假设种族会影响基因型分布,从而可能影响PCa的病因,甚至可能在不同种族群体中产生相反的影响。鉴于参与者数量较少,结果应在更大样本量上进行验证。

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