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HSD3B1 基因(rs6203 和 rs33937873)单核苷酸多态性在预测前列腺癌风险中的作用。

Role of single nucleotide polymorphisms of the HSD3B1 gene (rs6203 and rs33937873) in the prediction of prostate cancer risk.

机构信息

Department of Clinical and Chemical Pathology, Faculty of Medicine, Helwan University, Cairo 11795, Egypt.

Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Helwan University, Cairo 11795, Egypt.

出版信息

Mol Med Rep. 2022 Aug;26(2). doi: 10.3892/mmr.2022.12787. Epub 2022 Jul 7.

DOI:10.3892/mmr.2022.12787
PMID:35795973
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9309536/
Abstract

3‑β‑hydroxysteroid dehydrogenase 1 (HSD3B1) is shown to affect dihydrotestosterone level in prostatic tissue which is a risk factor for prostate cancer (PC). The present study aimed to determine whether rs33937873 (G313A) and rs6203 (C338T) single nucleotide polymorphisms (SNP) in HSD3B1 gene was a potential risk factor for PC susceptibility and can predict the recurrence of PC in Egyptian patients. A total of 186 Egyptian patients were selected with incident primary PC and compared with 180 age healthy controls. The frequencies and the main effect of rs33937873 and rs6203 in HSD3B1 were compared and investigated between the patients and control using genotyping technique and statistical analysis. The mutant GA genotype of G313A in rs33937873 SNP was considered as an independent risk for PC in the multivariate regression analysis [odds ratio (OR)=2.7, 95% confidence intervals (CI): 1.2‑5.5, P=0.01] together with positive history of hypertension (HTN) (OR=6.2, 95% CI: 3.2‑12.1, P=0.0001) and begin prostatic hyperplasia (BPH; OR=8.9, 95% CI: 4.5‑17.5, P=0.0001). Conversely, in rs6203 (C338T), C allele is considered as major risk allele in the development of PC (OR=1.8, 95% CI: 1.3‑2.4, P=0.0003). The univariate logistic regression analyses indicated that CC genotype of rs6203 was a PC risk factor (OR=1.9, 95% CI: 1.3‑2.9, P=0.002). In addition, the frequency of the A‑C haplotype established by rs33937873‑rs6203 was also significantly higher for PC (P=0.013). The predication of PC recurrence was associated only with positive family history (OR=7.7, 95% CI: 2.3‑25.9, P=0.001) and not for The G313A and C338T SNPs. These results suggested that the two HSD3B1 polymorphisms rs33937873 and rs6203 may modify the risk of PC, particularly among patients with HTN and history of BPH, suggesting them as prominent future markers for prediction of PC risk.

摘要

3-β-羟类固醇脱氢酶 1(HSD3B1)被证明会影响前列腺组织中二氢睾酮的水平,而二氢睾酮是前列腺癌(PC)的一个风险因素。本研究旨在确定 HSD3B1 基因中的 rs33937873(G313A)和 rs6203(C338T)单核苷酸多态性(SNP)是否是 PC 易感性的潜在危险因素,并能预测埃及患者 PC 的复发。选择了 186 名患有初发原发性 PC 的埃及患者,并与 180 名年龄匹配的健康对照进行比较。使用基因分型技术和统计分析比较了 rs33937873 和 rs6203 中 HSD3B1 的频率和主要效应。在多变量回归分析中,G313A 中的 GA 突变基因型被认为是 PC 的独立危险因素[比值比(OR)=2.7,95%置信区间(CI):1.2-5.5,P=0.01],同时还伴有高血压(HTN)阳性史(OR=6.2,95%CI:3.2-12.1,P=0.0001)和前列腺增生(BPH)病史(OR=8.9,95%CI:4.5-17.5,P=0.0001)。相反,在 rs6203(C338T)中,C 等位基因被认为是 PC 发病的主要风险等位基因(OR=1.8,95%CI:1.3-2.4,P=0.0003)。单变量 logistic 回归分析表明,rs6203 的 CC 基因型是 PC 的危险因素(OR=1.9,95%CI:1.3-2.9,P=0.002)。此外,由 rs33937873-rs6203 建立的 A-C 单倍型的频率也显著高于 PC(P=0.013)。PC 复发的预测仅与阳性家族史相关(OR=7.7,95%CI:2.3-25.9,P=0.001),而与 G313A 和 C338T SNPs 无关。这些结果表明,HSD3B1 的两个多态性 rs33937873 和 rs6203 可能改变 PC 的风险,特别是在高血压和 BPH 病史的患者中,表明它们是预测 PC 风险的重要候选标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a63/9309536/3595815b37f4/mmr-26-02-12787-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a63/9309536/3595815b37f4/mmr-26-02-12787-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a63/9309536/3595815b37f4/mmr-26-02-12787-g00.jpg

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