Genetic variants of the CYP1B1 gene as predictors of biochemical recurrence after radical prostatectomy in localized prostate cancer patients.
Genetic variants of the CYP1B1 gene as predictors of biochemical recurrence after radical prostatectomy in localized prostate cancer patients.
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CYP1B1基因的遗传变异作为局限性前列腺癌患者根治性前列腺切除术后生化复发的预测因子
DOI：
10.1097/md.0000000000004066
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发表时间：
2016-07
期刊：
影响因子：
1.6
通讯作者：
Ye DW
中科院分区：
文献类型：
--
作者：
Gu CY;Qin XJ;Qu YY;Zhu Y;Wan FN;Zhang GM;Sun LJ;Zhu Y;Ye DW
补充数字内容是可用的文本临床定位前列腺癌是治愈的。然而，许多患者在根治性前列腺切除术(RP)后发生了生化复发。越来越多的证据表明，雌激素和外源致癌物通过雌激素的氧化代谢在前列腺癌的进展中起着重要作用。CYP1B1是一种参与雌激素羟化的酶，这是一种与雌激素代谢密切相关的反应。鉴于CYP1B1在内源性/外源性雌激素及其化合物的氧化代谢中的作用，CYP1B1基因的多态有可能改变其表达，从而导致进展。我们假设，CYP1B1基因的遗传变异可能会影响临床局限性前列腺癌患者的临床结果。在这项队列研究中，我们对312例接受RP治疗的患者的9个标记单核苷酸多态(SNPs)进行了基因分型。为了进行复制，在426名患者的独立队列中对这些SNP进行了基因分型。采用逆转录和实时定量聚合酶链式反应检测癌旁正常前列腺组织中细胞色素P4501B1的表达水平。采用Kaplan-Meier分析和Cox比例风险模型确定与BCR相关的SNPs。CYP1B1rs1056836与BCR显著相关(危险比[HR]：0.69；95%可信区间[CI]：0.40~0.89，P=0.002)和相对表达。我们的发现表明，CYP1B1基因的遗传变异可能有助于临床局限性前列腺癌患者的不同临床结果。
Supplemental Digital Content is available in the text Clinically localized prostate cancer is curative. Nevertheless many patients suffered from biochemical recurrence (BCR) after radical prostatectomy (RP). Mounting evidence suggest that estrogen and xenobiotic carcinogens play an essential role in progression of prostate cancervia oxidative estrogen metabolism. CYP1B1 is an enzyme involved in the hydroxylation of estrogens, a reaction of key relevance in estrogen metabolism. Given the role of CYP1B1 in the oxidative metabolism of endogenous/exogenous estrogen and compounds, CYP1B1 polymorphisms have the potential to modify its expression and subsequently lead to progression. We hypothesize that genetic variants of the CYP1B1 gene may influence clinical outcome in clinically localized prostate cancer patients. In this cohort study, we genotyped 9 tagging single nucleotide polymorphisms (SNPs) from the CYP1B1 gene in 312 patients treated with RP. For replication, these SNPs were genotyped in an independent cohort of 426 patients. The expression level of CYP1B1 in the adjacent normal prostate tissues was quantified by reverse transcription and real-time polymerase chain reaction. Kaplan–Meier analysis and Cox proportional hazard models were utilized to identify SNPs that correlated with BCR. CYP1B1 rs1056836 was significantly associated with BCR (hazard ratio [HR]: 0.69; 95% confidence interval [CI]: 0.40–0.89, P = 0.002) and relative CYP1B1 mRNA expression. Our findings suggest inherited genetic variation in the CYP1B1 gene may contribute to variable clinical outcomes for patients with clinically localized prostate cancer.