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编码CYP1A2的基因中的多态性会影响前列腺癌的风险和进展。

Polymorphisms in the gene encoding CYP1A2 influence prostate cancer risk and progression.

作者信息

Vilčková Marta, Škereňová Mária, Dobrota Dušan, Kaplán Peter, Jurečeková Jana, Kliment Ján, Híveš Márk, Dušenka Róbert, Evin Daniel, Knoško Brožová Martina, Kmeťová Sivoňová Monika

机构信息

Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovak Republic.

Department of Clinical Biochemistry, Jessenius Faculty of Medicine and University Hospital Martin, Comenius University in Bratislava, 03601 Martin, Slovak Republic.

出版信息

Oncol Lett. 2023 Jan 16;25(2):85. doi: 10.3892/ol.2023.13671. eCollection 2023 Feb.

Abstract

The role of the cytochrome P450 1A2 () rs2472299, rs2470890 and rs11072508 polymorphisms in prostate cancer risk, disease progression and tumour development remains unclear. The potential associations of these three polymorphisms and haplotypes with prostate cancer susceptibility and its clinicopathological characteristics were therefore investigated. The present case-control study consisted of 522 patients with prostate cancer and 554 healthy controls. High-resolution melting analysis was used to determine the polymorphisms. No significant association in prostate cancer risk was seen for rs2472299 and rs11072508. However, a significantly decreased risk of prostate cancer was found for rs2470890 [odds ratio (OR), 0.67; P=0.02] in the recessive model. After analysis of the associations of clinical status and these three polymorphisms, the rs2470890 and rs11072508 polymorphisms showed a positive association with a higher Gleason score (rs2470890 OR, 1.36, P=0.04 in the allelic model; rs11072508 OR, 1.37, P=0.04 in the allelic model and OR, 1.60, P=0.03 in the dominant model). All three polymorphisms showed a significant positive association with pathological T stage in the additive, allelic and dominant genetic models (P<0.05). Haplotype analysis revealed that the most common haplotypes 'GTT' and 'ACC' were significantly associated with pathological T stages 3 and 4 (OR, 0.62; P=0.02 and OR, 1.54; P=0.03, respectively). A significant association was found between the 'GTT' haplotype and the Gleason score (OR, 0.71; P=0.03). In conclusion, these polymorphisms and haplotypes have the potential to predict prostate cancer disease progression.

摘要

细胞色素P450 1A2(CYP1A2)基因的rs2472299、rs2470890和rs11072508多态性在前列腺癌风险、疾病进展及肿瘤发生中的作用仍不明确。因此,研究了这三种多态性及单倍型与前列腺癌易感性及其临床病理特征之间的潜在关联。本病例对照研究纳入了522例前列腺癌患者和554例健康对照。采用高分辨率熔解分析确定CYP1A2基因多态性。rs2472299和rs11072508与前列腺癌风险无显著关联。然而,在隐性模型中,rs2470890的前列腺癌风险显著降低[比值比(OR),0.67;P = 0.02]。分析临床状态与这三种CYP1A2基因多态性的关联后发现,rs2470890和rs11072508多态性与较高的Gleason评分呈正相关(在等位基因模型中,rs2470890的OR为1.36,P = 0.04;rs11072508的OR为1.37,P = 0.04;在显性模型中,OR为1.60,P = 0.03)。在加性、等位基因和显性遗传模型中,所有三种多态性均与病理T分期呈显著正相关(P < 0.05)。单倍型分析显示,最常见的单倍型“GTT”和“ACC”分别与病理T分期3期和4期显著相关(OR分别为0.62;P = 0.02和OR为1.54;P = 0.03)。“GTT”单倍型与Gleason评分之间存在显著关联(OR为0.71;P = 0.03)。总之,这些CYP1A2基因多态性和单倍型具有预测前列腺癌疾病进展的潜力。

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